RARE DISEASE
Burkitt lymphoma
Burkitt lymphoma
Burkitt lymphoma
Synonyms: Small non-cleaved cell lymphoma
Synonyms: Small non-cleaved cell lymphoma
Synonyms: Small non-cleaved cell lymphoma
Drug discovery
4
drugs
With orphan designations
Overview
Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma characterized by MYC proto-oncogene translocations, with three clinical variants: endemic (linked to EBV/malaria in Africa), sporadic (non-African abdominal/lymph node involvement), and immunodeficiency-associated (HIV/organ transplant). Rapidly progressive, it requires urgent intensive chemotherapy (e.g., DA-EPOCH-R, CODOX-M/IVAC) with rituximab and central nervous system (CNS) prophylaxis. Cure rates exceed 90% in children and 70% in adults with early treatment, though outcomes decline in relapsed/refractory disease or older patients [1][8][13][16].
Population
Endemic peaks in African children (ages 4–7; male:female ratio 3:1) [2][17].
Sporadic accounts for 1–5% of adult NHL in Western countries, with median age 40–50 years [2][7][18].
Immunodeficiency-associated affects HIV/AIDS patients (30–40% of HIV-related lymphomas) and transplant recipients [1][6].
Burden
Cure rates: >90% in pediatric cases vs. 64% 2-year survival in adults, dropping to <40% in relapsed disease [1][7][12].
Global impact: 19,072 cases/year (2021), rising 207% since 1990; sub-Saharan Africa faces higher mortality due to limited access to intensive regimens [9][19].
Toxicity: Tumor lysis syndrome (25–50% incidence) and treatment-related mortality (10%) in adults highlight management challenges [1][4][16].
Therapies
First-line: Dose-adjusted EPOCH-R or R-CODOX-M/R-IVAC regimens + rituximab, with intrathecal methotrexate for CNS prophylaxis [1][8][16].
Risk stratification: Low-risk (localized) vs. high-risk (advanced/CNS involvement) guides therapy intensity [1][3].
Emerging options: Brentuximab vedotin, proteasome inhibitors, and CAR T-cell therapy under investigation for refractory cases [3][13].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
2,507 drug discovery papers about Burkitt lymphoma, with 6 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,507 drug discovery papers about Burkitt lymphoma, with 6 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-09-09 | Addition of Rituximab to First-Line Treatment of Burkitt Lymphoma in Children and Young Adults in Tanzania: A Cost-Utility Analysis.
Burkitt lymphoma (BL) is a highly prevalent childhood cancer in sub-Saharan Africa. Outcomes are poor, with only 50% 2-year survival. Improving survival through intensifying chemotherapy treatment has proved challenging. Incorporating rituximab (a high-cost biological agent) into the current chemotherapy regimen is an alternative approach. A recent observational study in Tanzania and Uganda found improved 1-year survival, with no significant additional adverse events, when rituximab was added to chemotherapy. We present an economic evaluation of this regimen compared with current treatment. We conducted a cost-utility analysis from a Tanzanian health care perspective, over a patient lifetime, using a 4-state Markov model. Outcomes were measured in Disability-Adjusted Life Years (DALYs), and results were compared with three possible cost-effectiveness thresholds ($411 US dollars [USD], $1,211 USD and $3,633 USD). Survival, adverse events, and chemotherapy use came from the observational study (N = 72). Other resource used was derived from treatment protocols and clinical expertise, and unit costs (2023) were provided by Tanzanian hospitals. Survival was modeled parametrically over 2 years, after which survivors were assumed to be cured. We examined heterogeneity in cost-effectiveness by disease stage and performed sensitivity and scenario analyses. Adding rituximab gave an incremental cost-effectiveness ratio (ICER) of $483 USD per DALY averted, slightly above the most stringent of the thresholds considered, and would be considered cost effective at any threshold above $501 USD. Rituximab was particularly cost effective in advanced-stage disease (ICER $395 USD). Results were sensitive to discount rate, drug costs particularly rituximab, and disease progression assumptions. Budget impact was estimated as Tanzanian Shillings 415 billion ($160 million USD) annually, from 5 years after implementation. Adding rituximab to current chemotherapy is a plausibly cost-effective treatment that would save lives in childhood BL, particularly for advanced-stage patients.
2026-07-22 | Glofitamab in the sequential treatment of relapsed/refractory B-Cell lymphoma: a single-center real-world study.
Glofitamab is a bispecific antibody (BsAb), and has good efficacy in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), especially in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). This study explored its sequential treatment strategies and efficacy in the real world, including rescue therapy after chimeric antigen receptor T cell (CAR-T) therapy failure, bridging CAR-T therapy and monotherapy. This was a single-center retrospective cohort analysis of 24 patients with clearly diagnosed relapsed/refractory B-cell lymphoma, including primary diffuse large B-cell lymphoma (DLBCL), diffuse large B-cell lymphoma with Richter transformation (DLBCL-RT), and Burkitt lymphoma (BL). Patients were divided into three groups according to the treatment sequence: Group 1 (Glofitamab rescue therapy after progression of CAR-T therapy), group 2 (Glofitamab bridging subsequent CAR-T therapy), and group 3 (Glofitamab monotherapy), who received Glofitamab at our center between September 2024 and December 2025. In the single-center real-world experience, Glofitamab demonstrated controllable safety and durable anti-tumor activity in three clinical scenarios. Especially, it could still bring clinical benefits even after CAR-T therapy failed, and it explored the sequential treatment strategy of Glofitamab and CAR-T.
2026-04-28 | Glofitamab in refractory Burkitt lymphoma‐type post‐transplant lymphoproliferative disorder
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
2026-03-27 | Pediatric Mandibular Burkitt Lymphoma Initially Misdiagnosed as Odontogenic Infection: A Radiologic-Pathologic Correlation
Burkitt lymphoma is a highly aggressive mature B-cell non-Hodgkin lymphoma characterized by MYC dysregulation and a high proliferative index. Although the sporadic form commonly presents with abdominal involvement, maxillofacial manifestations in children may mimic odontogenic infections, leading to delayed diagnosis. We report a nine-year-old boy with a rapidly progressive unilateral mandibular swelling initially treated as a dental abscess without improvement. Imaging revealed an ill-defined osteolytic mandibular lesion with cortical erosion and soft tissue extension, raising suspicion for malignancy. Histopathology demonstrated monomorphic medium-sized atypical lymphoid cells with high mitotic activity. Immunohistochemistry confirmed B-cell lineage (CD20, CD10, BCL6, c-MYC) with a Ki-67 index of 95%, consistent with Burkitt lymphoma. The patient was treated with rituximab-based multi-agent chemotherapy and showed a favorable response. This case highlights the importance of early radiologic-pathologic correlation and prompt biopsy in atypical pediatric mandibular swellings to enable timely diagnosis and management.
2026-03-05 | Case Report: Glofitamab in the treatment of a patient with central nervous system-involved Burkitt lymphoma.
Burkitt lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. While targeted combination chemotherapy can be effective, it is associated with a high rate of relapsed or refractory disease and a pronounced propensity for central nervous system (CNS) involvement. Currently, novel therapies such as chimeric antigen receptor T-cell (CAR-T) therapy have not demonstrated established efficacy in BL. Given the poor prognosis and the challenge of managing relapsed/refractory BL, the use of bispecific antibodies, specifically glofitamab, as employed in this case, has yielded a favorable therapeutic outcome. This is particularly noteworthy in the present case, given the patient's documented CNS infiltration. After the failure of first-line treatment in this case, the combination of glofitamab and a Bruton's tyrosine kinase inhibitor (BTKi) was used for six cycles, which significantly improved the patient's CNS infiltration and achieved a long remission period. This provides an opportunity to try glofitamab in the treatment of CNS lymphoma, and we look forward to its confirmation in more BL patients.
small molecules
2026-09-29 | Anti-tumor activity of valproic acid in EBV-positive Burkitt lymphoma via PFN2-associated PI3K/AKT pathway repression.
Burkitt lymphoma (BL) has limited therapies and poor prognosis in elderly or relapsed patients. Valproic acid (VPA) exhibits broad anti-tumor activity, but its quantitative efficacy and molecular mechanism in EBV-positive BL remain undefined. VPA activity in Daudi, Raji, Namalwa BL cell lines (n = 3 biological replicates per assay) was assessed using CCK-8 viability (24 h/48 h IC50 values), EdU proliferation, PI cell-cycle, and Annexin V/PI dual-staining apoptosis assays. In vivo efficacy was tested in Namalwa CDX (control n = 5, VPA n = 6) and three independent EBV-positive PDX models (6 mice/group for each PDX line), with daily 400 mg/kg intraperitoneal VPA administration for 1-3 weeks; ex vivo drug response of PDX fragments was quantified via hydrogel embedded histoculture drug sensitivity test (HDST). RNA-seq was conducted on PDX No.1 tumor tissues (VPA vs. saline control, n = 3 per group). PFN2 and PI3K/AKT pathway alterations were validated by RT-qPCR, Western blot, PFN2 knockdown/overexpression, and PI3K/AKT inhibitor combination assays. 24 h IC50 values of VPA were 20.15, 4.672, 7.769 mM for Daudi, Raji, Namalwa, while 48 h IC50 decreased to 4.891, 2.283, 0.4836 mM. At 2 mM VPA treatment for 24 h, total apoptosis rates increased by 14.22% (Daudi), 10.20% (Raji), and 18.68% (Namalwa). VPA induced G0/G1 cell-cycle arrest across all 3 cell lines. In CDX and three PDX models, VPA treatment reduced tumor weight (CDX: control 1.132 g vs. VPA 0.365 g, p = 0.0207, No.1: control 1.450 g vs. VPA 1.013 g, p = 0.049, No.2: control 1.283 g vs. VPA 0.913 g, p = 0.0295, No.3: control 1.371 g vs. VPA 0.9239, p = 0.0062) without body weight loss. RNA-seq analysis identified PFN2 as an exploratory candidate transcript with nominal transcriptional downregulation upon VPA administration (log2FC = -0.3213, raw p = 0.0355, FDR = 0.6149), and KEGG enrichment revealed perturbation of the PI3K/AKT signaling pathway. VPA reduced PFN2 mRNA and protein abundance in vitro and in vivo. PFN2 knockdown recapitulated proliferation suppression and reduced p-PI3K/p-AKT levels; PFN2 overexpression partially restored cell proliferation and PI3K/AKT phosphorylation, which could be attenuated by VPA treatment. Co-administration of VPA with idelalisib or capivasertib produced stronger anti-proliferative effects of BL. VPA exerts potent anti-tumor activity against EBV-positive BL in vitro and in multiple xenograft models, associated with PFN2 downregulation and suppressed PI3K/AKT signaling.
2026-09-07 | [From syndrome of inappropriate antidiuretic hormone secretion deficiency to excess - Challenges and solutions in a unique case].
Introduction: the sequential transition from central diabetes insipidus (CDI) to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an exceptionally rare condition and represents a major diagnostic and therapeutic challenge. Case report: we report the case of a 47-year-old man with Burkitt lymphoma involving the hypothalamic-pituitary region who initially presented with polyuria, polydipsia, and hypernatremia. CDI was confirmed by biochemical findings and a positive response to desmopressin. Following desmopressin treatment and intensive chemotherapy, rapid tumor regression and partial recovery of neurohypophyseal function were observed. During follow-up, the patient developed persistent euvolemic hyponatremia with low plasma osmolality, inappropriately concentrated urine, and elevated urinary sodium. After excluding adrenal insufficiency, hypothyroidism, desmopressin overtreatment, and other secondary causes, SIADH was diagnose. Discussion: this case highlights the rare sequential transition from ADH deficiency to ADH excess caused by the same hypothalamic-pituitary disease and supports oral urea as an effective, safe, and cost-effective therapeutic option for chronic SIADH.
2026-08-17 | Dual MYC and GSPT1 Protein Degrader for MYC-Driven Hematologic Malignancies.
Direct targeting of the oncoprotein MYC has not yet been successful. We here report a novel dual protein degrader, GT19630, which binds directly to MYC and G1 to S phase transition protein 1 (GSPT1). GT19630 disrupts a novel feedforward loop of MYC and GSPT1, where MYC promotes transcription of GSPT1, and GSPT1 senses the stop codon of MYC to properly terminate its translation. The agent induces integrated stress response and abrogates oxidative phosphorylation through inhibition of the TCA cycle, resulting in apoptosis. GT19630 has superior activity compared to GSPT1- targeting molecular glues. GT19630 induces profound anti-proliferative effects and apoptosis at low nanomolar concentrations in a multitude of leukemia and lymphoma cell lines and primary samples, including those with TP53 mutations. GT19630 is highly active in vivo in models of therapy-resistant hematologic malignancies, including Burkitt's lymphoma, acute myeloid leukemia (AML) and multiple myeloma. CD34+ AML blasts overexpress MYC protein compared to normal hematopoietic stem/progenitor cells (HSPCs) and GT19630 induces greater cytotoxicity in AML cells compared to normal HSPCs. Further, GT19630 restores sensitivity to venetoclax and profoundly prolongs survival in vivo in venetoclax-resistant AML. GT19630 was well tolerated in humanized Crbn mice. In conclusion, our data support the development of the MYC/GSPT1 degrader GT19630 as a therapeutic strategy of MYC-driven hematologic malignancies.
2026-08-11 | Inhibitory effect of iguratimod on Epstein-Barr virus production in Burkitt lymphoma cell line (AKATA) and B lymphoblastoid cells produced by in vitro transformation of Epstein-Barr virus.
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been implicated in Epstein-Barr virus (EBV) reactivation. In this study, we aimed to investigate the role of iguratimod, an NF-κB activator inhibitor, in EBV lytic cycle activation in EBV-infected cells. EBV-producing cells, AKATA, and B-lymphoblastoid cells (BLBC) with 1 μM iguratimod. EBV DNA copy numbers were measured using real-time polymerase chain reaction. The inhibitory effect of iguratimod on NF-κB nuclear translocation in AKATA cells was examined. Immunohistochemical staining revealed significantly increased EBV early antigen diffuse type (EA-D) production in IgG-stimulated AKATA cells and IgM-stimulated BLBC compared with unstimulated cells, whereas co-culture with iguratimod suppressed the production of EBV EA-D. Additionally, AKATA cells/BLBC stimulated with anti-human IgG/IgM showed a significant increase in EBV DNA copy number compared to unstimulated cells, which was significantly reduced by co-culture with iguratimod. Nuclear expression of NF-κB was observed in AKATA cells stimulated with anti-human IgG, and NF-κB expression was suppressed by treatment with iguratimod. These findings suggest that iguratimod may reduce rheumatoid arthritis disease activity by partially inhibiting EBV reactivation. This may partially suppress the onset of RA.
2026-08-07 | DNA Replication Stress-Induced Transcriptome of Human Burkitt's Lymphoma Identifies Reciprocal Regulation Between MBD1 and BCL6 During Germinal Center-Derived B-Lymphomagenesis.
BCL6 is a master transcriptional regulator of germinal center (GC) B cells. BCL6 is frequently translocated at the major translocation cluster (MTC) within intron 1 of the BCL6 locus, a hotspot commonly rearranged in diffuse large B cell lymphomas (DLBCLs). BCL6 amplifications are associated with therapeutic resistance and poor survival outcomes in hematological and solid cancers. However the mechanisms suppressing genome instability at the BCL6-MTC preventing BCL6 rearragements remain unclear. Here, transcriptome analysis and genome-wide mapping of histone H3 lysine 4 trimethylation (H3K4me3) in hydroxyurea (HU)-treated Raji cells (a Burkitt's lymphoma model) revealed the induced expression of MBD1, encoding the DNA CpG methylation-binding protein. Functional studies using shRNA silencing and ectopic overexpression demonstrated that MBD1 suppresses BCL6 transcription whose promoter harbors conserved CpG methylation sites, suggesting a DNA methylation-dependent regulation of BCL6 trasncription by MBD1. Conversely, BCL6 repressed MBD1 expression by binding to its promoter. MBD1-depleted Raji cells exhibited increased genomic instability at the BCL6-MTC upon HU treatment, heightened sensitivity to DNA replication inhibitors (HU, gemcitabine, and etoposide), and reduced tumorigenicity in xenograft mouse models. We propose that MBD1 prevents genomic instability at the BCL6-MTC to suppress DLBCL formation. Moreover, MBD1 promotes genomic stability and cell viability during DNA replication stress. MBD1 thus represents a potential therapeutic target for cancers exhibiting resistance to chemotherapies targeting DNA replication.
cell therapies
2026-07-14 | [Burkitt lymphoma: Definition, diagnostic approach, and current therapeutic strategies].
Burkitt lymphoma is a rare and highly aggressive B-cell disorder characterized by rapid proliferation, and a translocation involving the c-MYC gene. It affects patients of all ages. The association with Epstein-Barr virus is well established in the 2022 World Health Organization classification, which identifies two molecular subtypes independent of epidemiological context. Diagnosis relies on a combination of clinical, histological, and cytogenetic features, allowing differentiation from other high-grade B-cell lymphomas. Prompt therapeutic management is crucial. Frontline therapy is based on intensive chemo-immunotherapy regimens, including anti-CD20 monoclonal antibodies. In young patients, overall survival rates reach 80-90%. Poor prognosis is mainly observed in refractory or relapsed disease. Emerging therapeutic approaches such as cellular therapy (genetically modified T-cell receptor therapies), immunotherapy (bispecific antibodies), and targeted therapy - currently approved in other B-cell lymphomas, are under investigation in Burkitt lymphoma. This review summarizes the definition, historical background, diagnostic criteria, classification, and current therapeutic management of Burkitt lymphoma in 2025.
2026-07-06 | Tumor Lysis Syndrome Risk in Burkitt Lymphoma Versus Mantle Cell Lymphoma During Alkylating Therapy: A Propensity-Matched TriNetX Comparative Outcome Analysis.
Background Tumor lysis syndrome (TLS) is a preventable oncologic emergency that can rapidly progress to acute kidney injury, malignant arrhythmias, seizures, and death. Because key prevention decisions (prophylaxis intensity, monitoring frequency, and inpatient versus outpatient initiation) are made at the start of therapy, clinically useful risk estimates must separate intrinsic disease risk from regimen-driven risk. However, cross-histology TLS comparisons are frequently confounded by systematic differences in chemotherapy composition and intensity. We therefore evaluated whether Burkitt lymphoma retains a higher TLS risk than mantle cell lymphoma (MCL) under a treatment-restricted framework anchored to shared alkylating exposure, with the goal of generating practical clinical insight for early TLS risk recognition, prevention, and monitoring in real-world practice, including urgent and emergency care settings. Methods We performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated real-world electronic health record research platform. Two cohorts were constructed (Burkitt lymphoma and MCL) and restricted to patients with exposure to cyclophosphamide or ifosfamide. Identical exclusions were applied to both cohorts for anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin), immune checkpoint inhibitors (nivolumab and pembrolizumab), and lymphoma coded as "in remission." Outcomes were assessed beginning one day after cohort entry (index event). The primary outcome was TLS (ICD-10-CM E88.3). Propensity score matching was performed 1:1. Time-to-event analyses used Kaplan-Meier methods with log-rank testing. Results After propensity score matching, 290 patients were included in each cohort (290 matched pairs). TLS occurred in 10.0% of the Burkitt cohort (29/290) compared with 5.5% of the mantle cell cohort (16/290), corresponding to an absolute risk difference of 4.5% (95% CI 0.1-8.8%; p = 0.044). On a relative scale, Burkitt lymphoma was associated with higher TLS risk, with a risk ratio of 1.813 (95% CI 1.006-3.264) and an odds ratio of 1.903 (95% CI 1.010-3.585), indicating a consistent direction and magnitude of effect across measures. Time-to-event analyses were concordant with the risk-based estimates: Kaplan-Meier analysis demonstrated shorter TLS-free survival in the Burkitt cohort (log-rank p = 0.034; HR 1.915, 95% CI 1.039-3.527). Median TLS-free survival was not reached in either cohort within available follow-up. Conclusions In this propensity-matched real-world cohort restricted to cyclophosphamide/ifosfamide exposure and excluding anthracyclines and immune checkpoint inhibitors, Burkitt lymphoma was associated with higher TLS incidence and shorter TLS-free survival compared with MCL. These findings support classifying Burkitt lymphoma as a higher-risk phenotype at treatment initiation and adopting more intensive TLS prevention and monitoring strategies (particularly proactive hydration and closer biochemical surveillance) with escalation of urate-lowering therapy as indicated, consistent with established TLS risk frameworks.
2026-06-20 | Burkitt Lymphoma Unmasking HIV Infection Amid Multiple Life-Threatening Opportunistic Infections: A Case Report
Background: Burkitt lymphoma (BL) is an aggressive AIDS-defining B-cell non-Hodgkin lymphoma. Its simultaneous occurrence with severe opportunistic infections at HIV diagnosis represents an exceptional and life-threatening scenario. Case Presentation: A 36-year-old male with newly diagnosed HIV infection (viral load >10,000,000 copies/mL) presented simultaneously with invasive pulmonary aspergillosis, oropharyngeal-esophageal candidiasis, marked hepatic impairment, and a multinodular hepatic pattern with a suspicious pancreatic lesion on MRI. Inguinal lymph node biopsy confirmed Burkitt lymphoma with a starry-sky histological pattern. Liposomal amphotericin B was initiated first, followed by TDF/3TC/DTG antiretroviral therapy. After emergency transfer to hematology, the patient died approximately three weeks after chemotherapy initiation. Conclusion: This case highlights the exceptional prognostic severity of BL diagnosed concurrently with AIDS-defining opportunistic infections, and underscores the need for early HIV diagnosis, systematic lymph node biopsy in immunocompromised patients, and multidisciplinary management.
2026-06-10 | Childhood burkitt lymphoma: treatment outcomes, survival, and mortality predictors at two tertiary hospitals in Tanzania.
Burkitt lymphoma (BL) is an aggressive B-cell lymphoma predominantly affecting children in sub-Saharan Africa. It constitutes 50-70% of pediatric non-Hodgkin lymphomas in the region. In Tanzania, understanding the treatment outcomes and one-year survival rates at two major oncology centers can inform strategies to enhance survival. This retrospective cohort study analyzed children under 18 diagnosed with Burkitt lymphoma and treated at two tertiary care hospitals between January 2020 and December 2022. The study utilized Stata 18 to analyze data from medical records, focusing on demographic and clinical characteristics, Kaplan-Meier survival analysis, and Cox proportional hazards models to identify mortality predictors. The study analyzed 72 children with Burkitt lymphoma (mean age: 5.8 years), predominantly male (70.8%), with 52.8% from rural areas. Tumor sites were mainly mandibular (47.2%) and abdominal (41.7%). Treatment outcomes varied between hospitals: Kilimanjaro Christian Medical Centre had a higher complete remission rate (61.3%) compared to BMC (36.6%), while BMC experienced higher relapse (19.5%) and treatment abandonment rates (22.0%) than KCMC (6.5% and 3.2%, respectively). The one-year post-treatment survival rate was 75% overall, with a significantly longer mean survival time at KCMC (37.1 months) versus BMC (16.4 months). Key predictors of mortality included bone marrow involvement, adjusted hazard ratio (AHR) = 32.48 and CNS involvement (AHR = 34.00, 95% CI). The study reveals a 75% one-year survival rate for children with Burkitt lymphoma in Tanzania. However, this reflects short-term (one-year) survival and cannot be directly compared with the WHO Global Initiative for Childhood Cancer 2030 target, which refers to five-year overall survival. However, high treatment abandonment, relapse, and death rates, along with low complete remission rates, pose significant challenges. Key factors contributing to poor prognosis include CNS and bone marrow involvement. The study recommends comprehensive interventions, improved care access, and exploring alternative treatments like stem cell transplantation.
2026-06-03 | Shared clonal origin of angioimmunoblastic T-cell lymphoma and Burkitt lymphoma arising through divergent evolution from a common precursor.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type (AITL), is a common peripheral AQ1T-cell lymphoma characterized by recurrent mutations in TET2, IDH2, DNMT3A, and RHOA, with TET2 and DNMT3A mutations frequently arising in early hematopoietic stem and progenitor cells (HSPCs) as clonal hematopoiesis (CH). In addition to its well-established association with secondary myeloid neoplasms, AITL is complicated by secondary B-cell lymphomas in up to 10-23% of cases, often associated with EBV infection. However, the clonal relationship between AITL, CH, and associated B-cell lymphomas remains less well understood. We report a rare case of an elderly male who developed AITL followed by EBV-positive Burkitt lymphoma (BL) three years later. Comprehensive histopathologic evaluation, immunohistochemistry, flow cytometry, fluorescence in situ hybridization, and next-generation sequencing were performed on both lymphoma specimens and on a staging bone marrow sample. Molecular analysis revealed a shared TET2 p.Q962* mutation present at high variant allele frequencies in both the AITL and BL, which was also detected at low level in the bone marrow which showed no evidence of neoplasia, consistent with underlying CH. Each lymphoma harbored additional disease-characteristic genetic alterations, including RHOA mutation in AITL and MYC rearrangement with ID3 mutation in BL. This case establishes the shared clonal origin between AITL and BL arising in the setting of CH and provides additional biological insight into the development of B-cell lymphoma associated with AITL.
oligonucleotides
2025-10-31 | TIMAP downregulation in Burkitt's lymphoma reveals key molecules and signaling pathways in B-cell lymphomagenesis.
Burkitt's lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a regulatory subunit of protein phosphatase 1 catalytic subunit, enriched in lymphoid tissues, and upregulated in various cancers. Despite suggestions that TIMAP promotes lymphomagenesis in a c-myc-driven model, its precise role remains unclear. This study aimed to investigate the contribution of TIMAP to B-cell lymphomagenesis by examining transcriptomic changes upon TIMAP downregulation in BL cells. Raji BL cells were transfected with 2'Fluoro Arabinonucleic acid (FANA)-antisense oligonucleotides (ASO) targeting TIMAP (FANA-ASO-TIMAP) or a scramble control (FANA-ASO-Scramble). TIMAP expression was significantly reduced at the mRNA (0.70 ± 0.04, p = 0.001) and protein levels (median = 0.73, IQR = 0.13, p = 0.002). RNA sequencing identified 2,368 differentially expressed genes (DEGs), of which 1,326 were upregulated, and 1,042 were downregulated. Gene Ontology analysis revealed that the DEGs were primarily involved in cellular processes, DNA replication, intracellular signal transduction, and apoptosis. Pathways related to lymphoma progression, such as B-cell receptor signaling, p53 signaling, and mTOR signaling, were notably affected. Key genes such as PAK3, LINC00487, AID, PURPL, and BCL2 were among the most dysregulated, highlighting TIMAP's role in critical oncogenic pathways in B-cell Lymphoma. These findings suggest that TIMAP is a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis and could serve as a potential therapeutic target for novel treatments.
2025-10-27 | EBV-miR-BART5-3p promotes the proliferation of Burkitt lymphoma cells via glycolytic pathway.
Epstein-Barr virus is a double‑stranded DNA virus that plays a key role throughout the development of Burkitt lymphoma. The EBV genome encodes 44 mature microRNAs (miR‑BARTs) that collectively promote tumorigenesis. TP53, a tumor suppressor protein, prevents cancer progess by inducing cell-cycle arrest, apoptosis, and modulating glycolysis. In this study, we found that miR‑BART5‑3p is highly expressed in EBV positive cells and contributes to glycolysis process. Forced expression of miR‑BART5‑3p enhanced the proliferative and migratory capacities, while downregulation of miR‑BART5‑3p led to a reduction in these capacities in Ramos and CA46. Subsequently, we demonstrated that TP53 suppressed the proliferation and migration of Burkitt lymphoma cells. Furthermore, we predicted that EBV-miR‑BART5‑3p targeted 3'‑UTR of TP53 mRNA via RNAhybrid program and the QPCR results indicated that there was a significant converse expression between EBV-miR‑BART5‑3p and TP53 in Raji cells. These results implied that EBV-miR‑BART5‑3p promoted the proliferation of Ramos and CA46 via targeting the 3'‑UTR of TP53 mRNA. Altogether, these findings define a novel mechanism for EBV-miR-BART5-3p through the glycolysis pathway in Burkitt lymphoma development.
2025-09-25 | Abstract B049: Bispecific Aptamers for Enhanced Binding, Internalization, and Therapeutic Delivery in Burkitt Lymphoma
Abstract Burkitt lymphoma is an aggressive cancer that accounts for 30% of all pediatric lymphomas. Due to its aggressive clinical course, patients are immediately started on a high-intensity chemo-immunotherapy protocol with central nervous system (CNS) prophylaxis to prevent relapse or CNS involvement. The Magrath regimen (CODOX-M/IVAC – cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) is most commonly used for medical management, yielding two-year event-free survival rates as high as 90%. However, this drug regimen consists of nonspecific, broadly toxic medications and has frequently led to off-target toxicity. To prevent these unwanted effects, it is necessary to design a more targeted therapeutic that utilizes tumor-specific markers. Burkitt lymphoma cells (Ramos) have been shown to inappropriately display a component of the spliceosomal complex (hnRNP U) on their cell surface and many human tumors have been shown to overexpress the transferrin receptor (TfR) relative to native tissues, making these exciting targets. We aimed to produce dual-targeting aptamers and to characterize their binding to, internalization by, and therapeutic deliver to Ramos cells. Anti-hnRNP U DNA aptamer (c10.36) and an anti-TfR RNA aptamer (E3) each containing a 3’-terminal 21-nucleotide antitail or tail, respectively, were synthesized and annealed together using sense:antisense complexation. For fluorescent experiments, monospecific aptamers were annealed to a cyanine 3 (Cy3)-labelled antitail and bispecific aptamers were constructed using DNA aptamers with 3’ cy3 modification. Ramos cells were treated with bispecific, monospecific, or control aptamers for 1 hour prior to flow cytometric analysis or fixation, staining, and imaging by a confocal microscope. Ramos cells treated with c10.36-E3 bispecific aptamers demonstrated 9-fold higher fluorescence by flow cytometry relative to monospecific controls. Confocal microscopy showed greater fluorescent intensity and diffuse punctate staining pattern in Ramos cells treated with c10.36-E3 bispecific aptamers relative to their monospecific controls. In Ramos cells stained with LysoTracker dye, co-localization of c10.36-E3 bispecific aptamers with lysosomes was observed whereas this was not observed with control aptamers. When Ramos cells were pre-treated with endocytic inhibitors or transferrin, internalization of c10.36-E3 was found to be reduced by treatment with sucrose, low temperature, or human transferrin. Finally, Ramos cells were treated with on- or off-target bispecific aptamers containing 3’-Val-Cit-PABA-MMAF and viability was assessed using live-dead stain HelixNP via flow cytometry. Over 48 hours, c10.36-E3 led to dramatic reductions in viability relative to appropriate control products. In conclusion, the c10.36-E3 bispecific aptamer is internalized through TfR-mediated endocytosis with superior binding and trafficking relative to controls making it an exciting vehicle capable of targeted therapeutic delivery to Ramos cells. Citation Format: Joshua Shelton, Xue Bai, Brian J. Thomas, Agustin T. Barcellona, Donald H. Burke, Bret D. Ulery. Bispecific Aptamers for Enhanced Binding, Internalization, and Therapeutic Delivery in Burkitt Lymphoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr B049.
2025-01-10 | Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.
Over 90% of people are infected with the human g-herpesvirus known as the Epstein- Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt lymphoma, are thought to be linked with EBV. It is noteworthy that the first virus discovered that encodes microRNAs (miRNAs) was EBV, and these miRNAs show expression at the different phases of EBV infection. There is growing evidence that EBV-encoded miRNAs influence the growth of EBV-associated tumors. These EBV miRNAs, i.e., BamHI-H rightward fragment 1-derived microRNAs (BHRF1miRNA) and BamHI-A rightward fragment-derived microRNAs (BART miRNAs), are crucial for the persistence of viral infection and the avoidance of host defenses. Currently, significant advancements have been made in analyzing the microRNAs that are found in the duration of EBV infection, in vitro studies identified molecular targets of miRNAs and in vivo studies enhanced our understanding regarding the pathophysiology of these molecules. An extensive look into the pro-carcinogenic impact of microRNAs associated with EBV will increase our understanding of the molecular mechanisms of EBV-associated tumors. In this paper, we have highlighted the functions of miRNAs in EBV infection as well as recent developments in miRNA-based therapeutic and diagnostic approaches that could be useful for EBV-related malignancies. Significantly, targeted therapies against EBV miRNAs are advancing rapidly, with emerging approaches such as miRNA sponges, anti-miRNA oligonucleotides, and CRISPR/Cas9 technologies. These innovations indicate the imminent onset of a new era in the treatment of EBV-associated tumors.
2024-10-19 | From virus to cancer: Epstein-Barr virus miRNA connection in Burkitt's lymphoma.
In Burkitt's lymphoma (BL), Epstein-Barr virus-encoded microRNAs (EBV miRNAs) are emerging as crucial regulatory agents that impact cellular and viral gene regulation. This review investigates the multifaceted functions of EBV miRNAs in the pathogenesis of Burkitt lymphoma. EBV miRNAs regulate several cellular processes that are essential for BL development, such as apoptosis, immune evasion, and cellular proliferation. These small, non-coding RNAs target both viral and host mRNAs, finely adjusting the cellular environment to favor oncogenesis. Prominent miRNAs, such as BART (BamHI-A rightward transcript) and BHRF1 (BamHI fragment H rightward open reading frame 1), are emphasized for their roles in tumor growth and immune regulation. For example, BART miRNAs prevent apoptosis by suppressing pro-apoptotic proteins, whereas BHRF1 miRNAs promote viral latency and immunological evasion. Understanding the intricate connections among EBV miRNAs and their targets illuminates BL pathogenesis and suggests novel treatment approaches. Targeting EBV miRNAs or their specific pathways offers a feasible option for developing innovative therapies that aim to disrupt the carcinogenic processes initiated by these viral components. future studies should focus on precisely mapping miRNA‒target networks and developing miRNA-based diagnostic and therapeutic tools. This comprehensive article highlights the importance of EBV miRNAs in Burkitt lymphoma, indicating their potential as biomarkers and targets for innovative treatment strategies.
other
2026-07-30 | Malaria and cancer: common features and interactions.
Malaria and cancer are major global health burdens, causing high mortality. While often considered distinct, the two conditions share common features, including continuous cell replication within the body, systemic inflammation, immune modulation and evasion, metabolic reprogramming, endothelial dysfunction, and drug efflux mechanisms. Interestingly, whereas malaria parasite infection promotes Burkitt lymphoma, recent studies in animal models indicate that malaria may activate immune mechanisms against various tumors, thereby improving survival rates. The malaria protein VAR2CSA specifically binds to chondroitin sulfate A in the placenta and metastatic cancer cells, which can be exploited for cancer detection and treatment. Studying the common and unique features of malaria and cancer may facilitate the development of treatment strategies for both diseases.
2026-04-25 | Beyond the Usual Suspects: Emerging Associations Between Epstein-Barr Virus Infection/Infectious Mononucleosis and Cancers.
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus and a causal factor for Burkitt Lymphoma (BL), Hodgkin Lymphoma (HL), gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). Whether EBV contributes to a wider spectrum of cancers remains uncertain. We reviewed MEDLINE, Embase and Web of Science on 30th July 2024 to identify observational studies that examined the association between EBV infection or EBV-infectious mononucleosis (IM) and cancers beyond BL, HL, GC and NPC. Evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. For cancers meeting minimum thresholds we assessed etiologic fractions (EFs), biological plausibility, epidemiological burden, latency after IM, and predictive biomarkers. Thirty-three eligible studies were identified, yielding 13 hypotheses (i.e., specific potential reported associations between EBV infection or IM and individual cancer types) that advanced through GRADE. Breast cancer and NHL had the greatest weight of biological plausibility, cervical and prostate the least. Despite an array of tests, testicular cancer studies provided limited evidence. EFs ranged between 12.3% (IM-breast) and 85.1% (EBV infection-NHL). Breast and prostate cancers had the highest global incidence. Only one study (for NHL) provided data on time from IM to cancer onset, and prostate-specific antigen was the only biomarker identified. In this review, we highlight eight cancers across six cancer groups (breast, cervical, leukaemia/other haematologic, NHL, prostate, testicular) with some evidence of EBV involvement. These results reinforce the potential long-term value of EBV vaccine development, while emphasising the need for high-quality prospective studies with robust methods of viral detection to establish causality.
2025-12-25 | Dissecting Epstein-Barr Virus Dependence Across Diverse Infected Cell Models.
Epstein-Barr virus (EBV) is maintained clonally in a wide array of tumors and cells of lymphoproliferative disorders, yet the degree to which these infected cells continuously depend on EBV remains unresolved. To directly assess EBV dependence, we used two complementary Cas9-based viral eviction strategies: 1) targeting EBNA1 to promote episome dilution during cell division, and 2) targeting repetitive viral genomic regions to rapidly degrade EBV episomes. Using these approaches, we evaluated EBV-loss sensitivity across newly-derived, phenotypically diverse EBV-positive Burkitt lymphoma lines. We also evaluated cell lines from patients with EBV-associated T/NK and epithelial malignancies. We included the Burkitt Lymphoma cell line, Akata-GFP, as our EBV-loss-tolerant control and a lymphoblastoid cell line as our EBV-loss-sensitive control. We observed EBV-loss sensitivity in all the EBV-positive Burkitt Lymphoma cell lines and the chronic active EBV disease cell line. In contrast, the EBV-positive gastric adenocarcinoma lines were markedly less sensitive to EBV loss. EBV latency type did not predict EBV dependence, indicating that viral gene expression programs alone do not dictate reliance on the virus. These findings demonstrate that EBV dependence is prevalent across multiple EBV-associated disease models and is especially pronounced in early-state or newly derived lymphoid malignancies.
2025-12-01 | Abstract 60: Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa
Abstract Purpose: Epstein Barr virus (EBV) is a viral carcinogen associated with Burkitt lymphoma (BL), an aggressive lymphoma that is rare in the U.S. but responsible for most childhood cancer in the equatorial regions of sub-Saharan Africa. EBV is also associated with other cancers, including nasopharyngeal carcinoma in south Asia, some types of gastric cancer, and Hodgkin lymphoma, which contribute to about 2% of the global cancer burden. Discovery of antibody profiles associated with BL would provide new ways to investigate the biology of EBV-associated malignancies, design of screening or diagnostic assays, or develop targeted approaches for treatment. Here, we used an EBV proteome-wide assessment of seroprofiles against EBV in well-characterized cases and controls in the EMBLEM study. Methods: We measured antibody responses against a panel of 199 EBV recombinant proteins expressed from 5 EBV strains (48.2% ag876, 19.1% b958, 18.6% mutu, 9.6% akata, and raji 4.5%) in 701 BL cases and 700 age-, sex-, and area-frequency matched community controls from six regions Kenya, Tanzania, and Uganda. EBV peptide reactivity (standardized signal intensity, SSI) and positivity (number of positive peptides as defined as SSI ≥1) in cases and controls were compared via student’s unpaired t-tests and chi-squared test. Odds ratios of association and 95% confidence intervals were generated by logistic regression models, controlling for sex, country of origin, and by age group. Statistical significance was based on Bonferroni adjusted p-values. Results: Overall, BL cases were more likely to have higher mean (SD) peptide reactivity [case: 209.0 (25.5); control:198.1 (24.0); SSI, p=3.8e-16] and mean (SD) number of seropositive EBV peptides [case:95.9 (35.8); control: 83.0 (34.2); p=7.7e-12] as compared to controls. Total reactivity and seropositivity of peptides from all strains was significantly higher in cases as compared to controls, except for the Akata strain. We identified 66 peptides with mean values significantly higher in BL cases than controls after Bonferroni correction (range of ORs:1.53–4.07), of which 53 showed a significant trend (range of ORs: 1.27–2.28). These EBV peptides were mostly in the late lytic and latent stages of infection. Conclusion: Our results suggest that EBV peptides involved in both latency and lytic replication may influence BL pathogenesis, making them suitable targets for BL prevention and control. Citation Format: Jacquelyn R. Bedsaul-Fryer, Carla Proietti, Martin D. Ogwang, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert K. Tenge, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Hadijah Nabalende, Herry Dhudha, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Hyokyoung G. Hong, Denise Doolan, Sam M. Mbulaiteye. Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 60.
2025-10-29 | Finding the Sweet Spot for the Treatment of B Cell Malignancies.
The glycan profile of cells comprises a high variety of sugar moieties that are attached to proteins (glycoproteins) and lipids (glycolipids) via a process called 'glycosylation'. Cancer cells commonly carry aberrant glycans, which may be of interest for cancer diagnosis, prognosis, as well as the development of novel therapeutic strategies. This review focuses on the differential glycosylation patterns on malignant B cells, including both B cell lymphoma and leukemia. Well-known aberrant glycan profiles on malignant B cells include acquired high mannose N-glycans in the B cell receptor (BCR) of follicular lymphoma (FL), and increased expression of the glycosphingolipid Gb3/CD77 on Burkitt's lymphoma (BL). These structures can be exploited for therapy by using lectins that specifically recognize these patterns with intrinsic cytotoxic activity or in a drug-conjugate format. Furthermore, immunotherapy can be improved by modulating glycans, especially sialic acids. Targeting glycans for immunotherapy is also of interest for chimeric antigen receptor (CAR) T cell therapy, a relatively novel therapy that has been quite effective in various B cell malignancies. Thus, the glycan profile of malignant B cells harbors many opportunities for therapeutic targeting. It is anticipated that further in-depth glycan profiling will open up many more opportunities for the treatment of B cell malignancies.
antibodies
2026-09-09 | Addition of Rituximab to First-Line Treatment of Burkitt Lymphoma in Children and Young Adults in Tanzania: A Cost-Utility Analysis.
Burkitt lymphoma (BL) is a highly prevalent childhood cancer in sub-Saharan Africa. Outcomes are poor, with only 50% 2-year survival. Improving survival through intensifying chemotherapy treatment has proved challenging. Incorporating rituximab (a high-cost biological agent) into the current chemotherapy regimen is an alternative approach. A recent observational study in Tanzania and Uganda found improved 1-year survival, with no significant additional adverse events, when rituximab was added to chemotherapy. We present an economic evaluation of this regimen compared with current treatment. We conducted a cost-utility analysis from a Tanzanian health care perspective, over a patient lifetime, using a 4-state Markov model. Outcomes were measured in Disability-Adjusted Life Years (DALYs), and results were compared with three possible cost-effectiveness thresholds ($411 US dollars [USD], $1,211 USD and $3,633 USD). Survival, adverse events, and chemotherapy use came from the observational study (N = 72). Other resource used was derived from treatment protocols and clinical expertise, and unit costs (2023) were provided by Tanzanian hospitals. Survival was modeled parametrically over 2 years, after which survivors were assumed to be cured. We examined heterogeneity in cost-effectiveness by disease stage and performed sensitivity and scenario analyses. Adding rituximab gave an incremental cost-effectiveness ratio (ICER) of $483 USD per DALY averted, slightly above the most stringent of the thresholds considered, and would be considered cost effective at any threshold above $501 USD. Rituximab was particularly cost effective in advanced-stage disease (ICER $395 USD). Results were sensitive to discount rate, drug costs particularly rituximab, and disease progression assumptions. Budget impact was estimated as Tanzanian Shillings 415 billion ($160 million USD) annually, from 5 years after implementation. Adding rituximab to current chemotherapy is a plausibly cost-effective treatment that would save lives in childhood BL, particularly for advanced-stage patients.
2026-07-22 | Glofitamab in the sequential treatment of relapsed/refractory B-Cell lymphoma: a single-center real-world study.
Glofitamab is a bispecific antibody (BsAb), and has good efficacy in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), especially in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). This study explored its sequential treatment strategies and efficacy in the real world, including rescue therapy after chimeric antigen receptor T cell (CAR-T) therapy failure, bridging CAR-T therapy and monotherapy. This was a single-center retrospective cohort analysis of 24 patients with clearly diagnosed relapsed/refractory B-cell lymphoma, including primary diffuse large B-cell lymphoma (DLBCL), diffuse large B-cell lymphoma with Richter transformation (DLBCL-RT), and Burkitt lymphoma (BL). Patients were divided into three groups according to the treatment sequence: Group 1 (Glofitamab rescue therapy after progression of CAR-T therapy), group 2 (Glofitamab bridging subsequent CAR-T therapy), and group 3 (Glofitamab monotherapy), who received Glofitamab at our center between September 2024 and December 2025. In the single-center real-world experience, Glofitamab demonstrated controllable safety and durable anti-tumor activity in three clinical scenarios. Especially, it could still bring clinical benefits even after CAR-T therapy failed, and it explored the sequential treatment strategy of Glofitamab and CAR-T.
2026-04-28 | Glofitamab in refractory Burkitt lymphoma‐type post‐transplant lymphoproliferative disorder
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
2026-03-27 | Pediatric Mandibular Burkitt Lymphoma Initially Misdiagnosed as Odontogenic Infection: A Radiologic-Pathologic Correlation
Burkitt lymphoma is a highly aggressive mature B-cell non-Hodgkin lymphoma characterized by MYC dysregulation and a high proliferative index. Although the sporadic form commonly presents with abdominal involvement, maxillofacial manifestations in children may mimic odontogenic infections, leading to delayed diagnosis. We report a nine-year-old boy with a rapidly progressive unilateral mandibular swelling initially treated as a dental abscess without improvement. Imaging revealed an ill-defined osteolytic mandibular lesion with cortical erosion and soft tissue extension, raising suspicion for malignancy. Histopathology demonstrated monomorphic medium-sized atypical lymphoid cells with high mitotic activity. Immunohistochemistry confirmed B-cell lineage (CD20, CD10, BCL6, c-MYC) with a Ki-67 index of 95%, consistent with Burkitt lymphoma. The patient was treated with rituximab-based multi-agent chemotherapy and showed a favorable response. This case highlights the importance of early radiologic-pathologic correlation and prompt biopsy in atypical pediatric mandibular swellings to enable timely diagnosis and management.
2026-03-05 | Case Report: Glofitamab in the treatment of a patient with central nervous system-involved Burkitt lymphoma.
Burkitt lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. While targeted combination chemotherapy can be effective, it is associated with a high rate of relapsed or refractory disease and a pronounced propensity for central nervous system (CNS) involvement. Currently, novel therapies such as chimeric antigen receptor T-cell (CAR-T) therapy have not demonstrated established efficacy in BL. Given the poor prognosis and the challenge of managing relapsed/refractory BL, the use of bispecific antibodies, specifically glofitamab, as employed in this case, has yielded a favorable therapeutic outcome. This is particularly noteworthy in the present case, given the patient's documented CNS infiltration. After the failure of first-line treatment in this case, the combination of glofitamab and a Bruton's tyrosine kinase inhibitor (BTKi) was used for six cycles, which significantly improved the patient's CNS infiltration and achieved a long remission period. This provides an opportunity to try glofitamab in the treatment of CNS lymphoma, and we look forward to its confirmation in more BL patients.
small molecules
2026-09-29 | Anti-tumor activity of valproic acid in EBV-positive Burkitt lymphoma via PFN2-associated PI3K/AKT pathway repression.
Burkitt lymphoma (BL) has limited therapies and poor prognosis in elderly or relapsed patients. Valproic acid (VPA) exhibits broad anti-tumor activity, but its quantitative efficacy and molecular mechanism in EBV-positive BL remain undefined. VPA activity in Daudi, Raji, Namalwa BL cell lines (n = 3 biological replicates per assay) was assessed using CCK-8 viability (24 h/48 h IC50 values), EdU proliferation, PI cell-cycle, and Annexin V/PI dual-staining apoptosis assays. In vivo efficacy was tested in Namalwa CDX (control n = 5, VPA n = 6) and three independent EBV-positive PDX models (6 mice/group for each PDX line), with daily 400 mg/kg intraperitoneal VPA administration for 1-3 weeks; ex vivo drug response of PDX fragments was quantified via hydrogel embedded histoculture drug sensitivity test (HDST). RNA-seq was conducted on PDX No.1 tumor tissues (VPA vs. saline control, n = 3 per group). PFN2 and PI3K/AKT pathway alterations were validated by RT-qPCR, Western blot, PFN2 knockdown/overexpression, and PI3K/AKT inhibitor combination assays. 24 h IC50 values of VPA were 20.15, 4.672, 7.769 mM for Daudi, Raji, Namalwa, while 48 h IC50 decreased to 4.891, 2.283, 0.4836 mM. At 2 mM VPA treatment for 24 h, total apoptosis rates increased by 14.22% (Daudi), 10.20% (Raji), and 18.68% (Namalwa). VPA induced G0/G1 cell-cycle arrest across all 3 cell lines. In CDX and three PDX models, VPA treatment reduced tumor weight (CDX: control 1.132 g vs. VPA 0.365 g, p = 0.0207, No.1: control 1.450 g vs. VPA 1.013 g, p = 0.049, No.2: control 1.283 g vs. VPA 0.913 g, p = 0.0295, No.3: control 1.371 g vs. VPA 0.9239, p = 0.0062) without body weight loss. RNA-seq analysis identified PFN2 as an exploratory candidate transcript with nominal transcriptional downregulation upon VPA administration (log2FC = -0.3213, raw p = 0.0355, FDR = 0.6149), and KEGG enrichment revealed perturbation of the PI3K/AKT signaling pathway. VPA reduced PFN2 mRNA and protein abundance in vitro and in vivo. PFN2 knockdown recapitulated proliferation suppression and reduced p-PI3K/p-AKT levels; PFN2 overexpression partially restored cell proliferation and PI3K/AKT phosphorylation, which could be attenuated by VPA treatment. Co-administration of VPA with idelalisib or capivasertib produced stronger anti-proliferative effects of BL. VPA exerts potent anti-tumor activity against EBV-positive BL in vitro and in multiple xenograft models, associated with PFN2 downregulation and suppressed PI3K/AKT signaling.
2026-09-07 | [From syndrome of inappropriate antidiuretic hormone secretion deficiency to excess - Challenges and solutions in a unique case].
Introduction: the sequential transition from central diabetes insipidus (CDI) to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an exceptionally rare condition and represents a major diagnostic and therapeutic challenge. Case report: we report the case of a 47-year-old man with Burkitt lymphoma involving the hypothalamic-pituitary region who initially presented with polyuria, polydipsia, and hypernatremia. CDI was confirmed by biochemical findings and a positive response to desmopressin. Following desmopressin treatment and intensive chemotherapy, rapid tumor regression and partial recovery of neurohypophyseal function were observed. During follow-up, the patient developed persistent euvolemic hyponatremia with low plasma osmolality, inappropriately concentrated urine, and elevated urinary sodium. After excluding adrenal insufficiency, hypothyroidism, desmopressin overtreatment, and other secondary causes, SIADH was diagnose. Discussion: this case highlights the rare sequential transition from ADH deficiency to ADH excess caused by the same hypothalamic-pituitary disease and supports oral urea as an effective, safe, and cost-effective therapeutic option for chronic SIADH.
2026-08-17 | Dual MYC and GSPT1 Protein Degrader for MYC-Driven Hematologic Malignancies.
Direct targeting of the oncoprotein MYC has not yet been successful. We here report a novel dual protein degrader, GT19630, which binds directly to MYC and G1 to S phase transition protein 1 (GSPT1). GT19630 disrupts a novel feedforward loop of MYC and GSPT1, where MYC promotes transcription of GSPT1, and GSPT1 senses the stop codon of MYC to properly terminate its translation. The agent induces integrated stress response and abrogates oxidative phosphorylation through inhibition of the TCA cycle, resulting in apoptosis. GT19630 has superior activity compared to GSPT1- targeting molecular glues. GT19630 induces profound anti-proliferative effects and apoptosis at low nanomolar concentrations in a multitude of leukemia and lymphoma cell lines and primary samples, including those with TP53 mutations. GT19630 is highly active in vivo in models of therapy-resistant hematologic malignancies, including Burkitt's lymphoma, acute myeloid leukemia (AML) and multiple myeloma. CD34+ AML blasts overexpress MYC protein compared to normal hematopoietic stem/progenitor cells (HSPCs) and GT19630 induces greater cytotoxicity in AML cells compared to normal HSPCs. Further, GT19630 restores sensitivity to venetoclax and profoundly prolongs survival in vivo in venetoclax-resistant AML. GT19630 was well tolerated in humanized Crbn mice. In conclusion, our data support the development of the MYC/GSPT1 degrader GT19630 as a therapeutic strategy of MYC-driven hematologic malignancies.
2026-08-11 | Inhibitory effect of iguratimod on Epstein-Barr virus production in Burkitt lymphoma cell line (AKATA) and B lymphoblastoid cells produced by in vitro transformation of Epstein-Barr virus.
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been implicated in Epstein-Barr virus (EBV) reactivation. In this study, we aimed to investigate the role of iguratimod, an NF-κB activator inhibitor, in EBV lytic cycle activation in EBV-infected cells. EBV-producing cells, AKATA, and B-lymphoblastoid cells (BLBC) with 1 μM iguratimod. EBV DNA copy numbers were measured using real-time polymerase chain reaction. The inhibitory effect of iguratimod on NF-κB nuclear translocation in AKATA cells was examined. Immunohistochemical staining revealed significantly increased EBV early antigen diffuse type (EA-D) production in IgG-stimulated AKATA cells and IgM-stimulated BLBC compared with unstimulated cells, whereas co-culture with iguratimod suppressed the production of EBV EA-D. Additionally, AKATA cells/BLBC stimulated with anti-human IgG/IgM showed a significant increase in EBV DNA copy number compared to unstimulated cells, which was significantly reduced by co-culture with iguratimod. Nuclear expression of NF-κB was observed in AKATA cells stimulated with anti-human IgG, and NF-κB expression was suppressed by treatment with iguratimod. These findings suggest that iguratimod may reduce rheumatoid arthritis disease activity by partially inhibiting EBV reactivation. This may partially suppress the onset of RA.
2026-08-07 | DNA Replication Stress-Induced Transcriptome of Human Burkitt's Lymphoma Identifies Reciprocal Regulation Between MBD1 and BCL6 During Germinal Center-Derived B-Lymphomagenesis.
BCL6 is a master transcriptional regulator of germinal center (GC) B cells. BCL6 is frequently translocated at the major translocation cluster (MTC) within intron 1 of the BCL6 locus, a hotspot commonly rearranged in diffuse large B cell lymphomas (DLBCLs). BCL6 amplifications are associated with therapeutic resistance and poor survival outcomes in hematological and solid cancers. However the mechanisms suppressing genome instability at the BCL6-MTC preventing BCL6 rearragements remain unclear. Here, transcriptome analysis and genome-wide mapping of histone H3 lysine 4 trimethylation (H3K4me3) in hydroxyurea (HU)-treated Raji cells (a Burkitt's lymphoma model) revealed the induced expression of MBD1, encoding the DNA CpG methylation-binding protein. Functional studies using shRNA silencing and ectopic overexpression demonstrated that MBD1 suppresses BCL6 transcription whose promoter harbors conserved CpG methylation sites, suggesting a DNA methylation-dependent regulation of BCL6 trasncription by MBD1. Conversely, BCL6 repressed MBD1 expression by binding to its promoter. MBD1-depleted Raji cells exhibited increased genomic instability at the BCL6-MTC upon HU treatment, heightened sensitivity to DNA replication inhibitors (HU, gemcitabine, and etoposide), and reduced tumorigenicity in xenograft mouse models. We propose that MBD1 prevents genomic instability at the BCL6-MTC to suppress DLBCL formation. Moreover, MBD1 promotes genomic stability and cell viability during DNA replication stress. MBD1 thus represents a potential therapeutic target for cancers exhibiting resistance to chemotherapies targeting DNA replication.
cell therapies
2026-07-14 | [Burkitt lymphoma: Definition, diagnostic approach, and current therapeutic strategies].
Burkitt lymphoma is a rare and highly aggressive B-cell disorder characterized by rapid proliferation, and a translocation involving the c-MYC gene. It affects patients of all ages. The association with Epstein-Barr virus is well established in the 2022 World Health Organization classification, which identifies two molecular subtypes independent of epidemiological context. Diagnosis relies on a combination of clinical, histological, and cytogenetic features, allowing differentiation from other high-grade B-cell lymphomas. Prompt therapeutic management is crucial. Frontline therapy is based on intensive chemo-immunotherapy regimens, including anti-CD20 monoclonal antibodies. In young patients, overall survival rates reach 80-90%. Poor prognosis is mainly observed in refractory or relapsed disease. Emerging therapeutic approaches such as cellular therapy (genetically modified T-cell receptor therapies), immunotherapy (bispecific antibodies), and targeted therapy - currently approved in other B-cell lymphomas, are under investigation in Burkitt lymphoma. This review summarizes the definition, historical background, diagnostic criteria, classification, and current therapeutic management of Burkitt lymphoma in 2025.
2026-07-06 | Tumor Lysis Syndrome Risk in Burkitt Lymphoma Versus Mantle Cell Lymphoma During Alkylating Therapy: A Propensity-Matched TriNetX Comparative Outcome Analysis.
Background Tumor lysis syndrome (TLS) is a preventable oncologic emergency that can rapidly progress to acute kidney injury, malignant arrhythmias, seizures, and death. Because key prevention decisions (prophylaxis intensity, monitoring frequency, and inpatient versus outpatient initiation) are made at the start of therapy, clinically useful risk estimates must separate intrinsic disease risk from regimen-driven risk. However, cross-histology TLS comparisons are frequently confounded by systematic differences in chemotherapy composition and intensity. We therefore evaluated whether Burkitt lymphoma retains a higher TLS risk than mantle cell lymphoma (MCL) under a treatment-restricted framework anchored to shared alkylating exposure, with the goal of generating practical clinical insight for early TLS risk recognition, prevention, and monitoring in real-world practice, including urgent and emergency care settings. Methods We performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated real-world electronic health record research platform. Two cohorts were constructed (Burkitt lymphoma and MCL) and restricted to patients with exposure to cyclophosphamide or ifosfamide. Identical exclusions were applied to both cohorts for anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin), immune checkpoint inhibitors (nivolumab and pembrolizumab), and lymphoma coded as "in remission." Outcomes were assessed beginning one day after cohort entry (index event). The primary outcome was TLS (ICD-10-CM E88.3). Propensity score matching was performed 1:1. Time-to-event analyses used Kaplan-Meier methods with log-rank testing. Results After propensity score matching, 290 patients were included in each cohort (290 matched pairs). TLS occurred in 10.0% of the Burkitt cohort (29/290) compared with 5.5% of the mantle cell cohort (16/290), corresponding to an absolute risk difference of 4.5% (95% CI 0.1-8.8%; p = 0.044). On a relative scale, Burkitt lymphoma was associated with higher TLS risk, with a risk ratio of 1.813 (95% CI 1.006-3.264) and an odds ratio of 1.903 (95% CI 1.010-3.585), indicating a consistent direction and magnitude of effect across measures. Time-to-event analyses were concordant with the risk-based estimates: Kaplan-Meier analysis demonstrated shorter TLS-free survival in the Burkitt cohort (log-rank p = 0.034; HR 1.915, 95% CI 1.039-3.527). Median TLS-free survival was not reached in either cohort within available follow-up. Conclusions In this propensity-matched real-world cohort restricted to cyclophosphamide/ifosfamide exposure and excluding anthracyclines and immune checkpoint inhibitors, Burkitt lymphoma was associated with higher TLS incidence and shorter TLS-free survival compared with MCL. These findings support classifying Burkitt lymphoma as a higher-risk phenotype at treatment initiation and adopting more intensive TLS prevention and monitoring strategies (particularly proactive hydration and closer biochemical surveillance) with escalation of urate-lowering therapy as indicated, consistent with established TLS risk frameworks.
2026-06-20 | Burkitt Lymphoma Unmasking HIV Infection Amid Multiple Life-Threatening Opportunistic Infections: A Case Report
Background: Burkitt lymphoma (BL) is an aggressive AIDS-defining B-cell non-Hodgkin lymphoma. Its simultaneous occurrence with severe opportunistic infections at HIV diagnosis represents an exceptional and life-threatening scenario. Case Presentation: A 36-year-old male with newly diagnosed HIV infection (viral load >10,000,000 copies/mL) presented simultaneously with invasive pulmonary aspergillosis, oropharyngeal-esophageal candidiasis, marked hepatic impairment, and a multinodular hepatic pattern with a suspicious pancreatic lesion on MRI. Inguinal lymph node biopsy confirmed Burkitt lymphoma with a starry-sky histological pattern. Liposomal amphotericin B was initiated first, followed by TDF/3TC/DTG antiretroviral therapy. After emergency transfer to hematology, the patient died approximately three weeks after chemotherapy initiation. Conclusion: This case highlights the exceptional prognostic severity of BL diagnosed concurrently with AIDS-defining opportunistic infections, and underscores the need for early HIV diagnosis, systematic lymph node biopsy in immunocompromised patients, and multidisciplinary management.
2026-06-10 | Childhood burkitt lymphoma: treatment outcomes, survival, and mortality predictors at two tertiary hospitals in Tanzania.
Burkitt lymphoma (BL) is an aggressive B-cell lymphoma predominantly affecting children in sub-Saharan Africa. It constitutes 50-70% of pediatric non-Hodgkin lymphomas in the region. In Tanzania, understanding the treatment outcomes and one-year survival rates at two major oncology centers can inform strategies to enhance survival. This retrospective cohort study analyzed children under 18 diagnosed with Burkitt lymphoma and treated at two tertiary care hospitals between January 2020 and December 2022. The study utilized Stata 18 to analyze data from medical records, focusing on demographic and clinical characteristics, Kaplan-Meier survival analysis, and Cox proportional hazards models to identify mortality predictors. The study analyzed 72 children with Burkitt lymphoma (mean age: 5.8 years), predominantly male (70.8%), with 52.8% from rural areas. Tumor sites were mainly mandibular (47.2%) and abdominal (41.7%). Treatment outcomes varied between hospitals: Kilimanjaro Christian Medical Centre had a higher complete remission rate (61.3%) compared to BMC (36.6%), while BMC experienced higher relapse (19.5%) and treatment abandonment rates (22.0%) than KCMC (6.5% and 3.2%, respectively). The one-year post-treatment survival rate was 75% overall, with a significantly longer mean survival time at KCMC (37.1 months) versus BMC (16.4 months). Key predictors of mortality included bone marrow involvement, adjusted hazard ratio (AHR) = 32.48 and CNS involvement (AHR = 34.00, 95% CI). The study reveals a 75% one-year survival rate for children with Burkitt lymphoma in Tanzania. However, this reflects short-term (one-year) survival and cannot be directly compared with the WHO Global Initiative for Childhood Cancer 2030 target, which refers to five-year overall survival. However, high treatment abandonment, relapse, and death rates, along with low complete remission rates, pose significant challenges. Key factors contributing to poor prognosis include CNS and bone marrow involvement. The study recommends comprehensive interventions, improved care access, and exploring alternative treatments like stem cell transplantation.
2026-06-03 | Shared clonal origin of angioimmunoblastic T-cell lymphoma and Burkitt lymphoma arising through divergent evolution from a common precursor.
Nodal T follicular helper cell lymphoma, angioimmunoblastic type (AITL), is a common peripheral AQ1T-cell lymphoma characterized by recurrent mutations in TET2, IDH2, DNMT3A, and RHOA, with TET2 and DNMT3A mutations frequently arising in early hematopoietic stem and progenitor cells (HSPCs) as clonal hematopoiesis (CH). In addition to its well-established association with secondary myeloid neoplasms, AITL is complicated by secondary B-cell lymphomas in up to 10-23% of cases, often associated with EBV infection. However, the clonal relationship between AITL, CH, and associated B-cell lymphomas remains less well understood. We report a rare case of an elderly male who developed AITL followed by EBV-positive Burkitt lymphoma (BL) three years later. Comprehensive histopathologic evaluation, immunohistochemistry, flow cytometry, fluorescence in situ hybridization, and next-generation sequencing were performed on both lymphoma specimens and on a staging bone marrow sample. Molecular analysis revealed a shared TET2 p.Q962* mutation present at high variant allele frequencies in both the AITL and BL, which was also detected at low level in the bone marrow which showed no evidence of neoplasia, consistent with underlying CH. Each lymphoma harbored additional disease-characteristic genetic alterations, including RHOA mutation in AITL and MYC rearrangement with ID3 mutation in BL. This case establishes the shared clonal origin between AITL and BL arising in the setting of CH and provides additional biological insight into the development of B-cell lymphoma associated with AITL.
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2025-10-31 | TIMAP downregulation in Burkitt's lymphoma reveals key molecules and signaling pathways in B-cell lymphomagenesis.
Burkitt's lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a regulatory subunit of protein phosphatase 1 catalytic subunit, enriched in lymphoid tissues, and upregulated in various cancers. Despite suggestions that TIMAP promotes lymphomagenesis in a c-myc-driven model, its precise role remains unclear. This study aimed to investigate the contribution of TIMAP to B-cell lymphomagenesis by examining transcriptomic changes upon TIMAP downregulation in BL cells. Raji BL cells were transfected with 2'Fluoro Arabinonucleic acid (FANA)-antisense oligonucleotides (ASO) targeting TIMAP (FANA-ASO-TIMAP) or a scramble control (FANA-ASO-Scramble). TIMAP expression was significantly reduced at the mRNA (0.70 ± 0.04, p = 0.001) and protein levels (median = 0.73, IQR = 0.13, p = 0.002). RNA sequencing identified 2,368 differentially expressed genes (DEGs), of which 1,326 were upregulated, and 1,042 were downregulated. Gene Ontology analysis revealed that the DEGs were primarily involved in cellular processes, DNA replication, intracellular signal transduction, and apoptosis. Pathways related to lymphoma progression, such as B-cell receptor signaling, p53 signaling, and mTOR signaling, were notably affected. Key genes such as PAK3, LINC00487, AID, PURPL, and BCL2 were among the most dysregulated, highlighting TIMAP's role in critical oncogenic pathways in B-cell Lymphoma. These findings suggest that TIMAP is a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis and could serve as a potential therapeutic target for novel treatments.
2025-10-27 | EBV-miR-BART5-3p promotes the proliferation of Burkitt lymphoma cells via glycolytic pathway.
Epstein-Barr virus is a double‑stranded DNA virus that plays a key role throughout the development of Burkitt lymphoma. The EBV genome encodes 44 mature microRNAs (miR‑BARTs) that collectively promote tumorigenesis. TP53, a tumor suppressor protein, prevents cancer progess by inducing cell-cycle arrest, apoptosis, and modulating glycolysis. In this study, we found that miR‑BART5‑3p is highly expressed in EBV positive cells and contributes to glycolysis process. Forced expression of miR‑BART5‑3p enhanced the proliferative and migratory capacities, while downregulation of miR‑BART5‑3p led to a reduction in these capacities in Ramos and CA46. Subsequently, we demonstrated that TP53 suppressed the proliferation and migration of Burkitt lymphoma cells. Furthermore, we predicted that EBV-miR‑BART5‑3p targeted 3'‑UTR of TP53 mRNA via RNAhybrid program and the QPCR results indicated that there was a significant converse expression between EBV-miR‑BART5‑3p and TP53 in Raji cells. These results implied that EBV-miR‑BART5‑3p promoted the proliferation of Ramos and CA46 via targeting the 3'‑UTR of TP53 mRNA. Altogether, these findings define a novel mechanism for EBV-miR-BART5-3p through the glycolysis pathway in Burkitt lymphoma development.
2025-09-25 | Abstract B049: Bispecific Aptamers for Enhanced Binding, Internalization, and Therapeutic Delivery in Burkitt Lymphoma
Abstract Burkitt lymphoma is an aggressive cancer that accounts for 30% of all pediatric lymphomas. Due to its aggressive clinical course, patients are immediately started on a high-intensity chemo-immunotherapy protocol with central nervous system (CNS) prophylaxis to prevent relapse or CNS involvement. The Magrath regimen (CODOX-M/IVAC – cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) is most commonly used for medical management, yielding two-year event-free survival rates as high as 90%. However, this drug regimen consists of nonspecific, broadly toxic medications and has frequently led to off-target toxicity. To prevent these unwanted effects, it is necessary to design a more targeted therapeutic that utilizes tumor-specific markers. Burkitt lymphoma cells (Ramos) have been shown to inappropriately display a component of the spliceosomal complex (hnRNP U) on their cell surface and many human tumors have been shown to overexpress the transferrin receptor (TfR) relative to native tissues, making these exciting targets. We aimed to produce dual-targeting aptamers and to characterize their binding to, internalization by, and therapeutic deliver to Ramos cells. Anti-hnRNP U DNA aptamer (c10.36) and an anti-TfR RNA aptamer (E3) each containing a 3’-terminal 21-nucleotide antitail or tail, respectively, were synthesized and annealed together using sense:antisense complexation. For fluorescent experiments, monospecific aptamers were annealed to a cyanine 3 (Cy3)-labelled antitail and bispecific aptamers were constructed using DNA aptamers with 3’ cy3 modification. Ramos cells were treated with bispecific, monospecific, or control aptamers for 1 hour prior to flow cytometric analysis or fixation, staining, and imaging by a confocal microscope. Ramos cells treated with c10.36-E3 bispecific aptamers demonstrated 9-fold higher fluorescence by flow cytometry relative to monospecific controls. Confocal microscopy showed greater fluorescent intensity and diffuse punctate staining pattern in Ramos cells treated with c10.36-E3 bispecific aptamers relative to their monospecific controls. In Ramos cells stained with LysoTracker dye, co-localization of c10.36-E3 bispecific aptamers with lysosomes was observed whereas this was not observed with control aptamers. When Ramos cells were pre-treated with endocytic inhibitors or transferrin, internalization of c10.36-E3 was found to be reduced by treatment with sucrose, low temperature, or human transferrin. Finally, Ramos cells were treated with on- or off-target bispecific aptamers containing 3’-Val-Cit-PABA-MMAF and viability was assessed using live-dead stain HelixNP via flow cytometry. Over 48 hours, c10.36-E3 led to dramatic reductions in viability relative to appropriate control products. In conclusion, the c10.36-E3 bispecific aptamer is internalized through TfR-mediated endocytosis with superior binding and trafficking relative to controls making it an exciting vehicle capable of targeted therapeutic delivery to Ramos cells. Citation Format: Joshua Shelton, Xue Bai, Brian J. Thomas, Agustin T. Barcellona, Donald H. Burke, Bret D. Ulery. Bispecific Aptamers for Enhanced Binding, Internalization, and Therapeutic Delivery in Burkitt Lymphoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr B049.
2025-01-10 | Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.
Over 90% of people are infected with the human g-herpesvirus known as the Epstein- Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt lymphoma, are thought to be linked with EBV. It is noteworthy that the first virus discovered that encodes microRNAs (miRNAs) was EBV, and these miRNAs show expression at the different phases of EBV infection. There is growing evidence that EBV-encoded miRNAs influence the growth of EBV-associated tumors. These EBV miRNAs, i.e., BamHI-H rightward fragment 1-derived microRNAs (BHRF1miRNA) and BamHI-A rightward fragment-derived microRNAs (BART miRNAs), are crucial for the persistence of viral infection and the avoidance of host defenses. Currently, significant advancements have been made in analyzing the microRNAs that are found in the duration of EBV infection, in vitro studies identified molecular targets of miRNAs and in vivo studies enhanced our understanding regarding the pathophysiology of these molecules. An extensive look into the pro-carcinogenic impact of microRNAs associated with EBV will increase our understanding of the molecular mechanisms of EBV-associated tumors. In this paper, we have highlighted the functions of miRNAs in EBV infection as well as recent developments in miRNA-based therapeutic and diagnostic approaches that could be useful for EBV-related malignancies. Significantly, targeted therapies against EBV miRNAs are advancing rapidly, with emerging approaches such as miRNA sponges, anti-miRNA oligonucleotides, and CRISPR/Cas9 technologies. These innovations indicate the imminent onset of a new era in the treatment of EBV-associated tumors.
2024-10-19 | From virus to cancer: Epstein-Barr virus miRNA connection in Burkitt's lymphoma.
In Burkitt's lymphoma (BL), Epstein-Barr virus-encoded microRNAs (EBV miRNAs) are emerging as crucial regulatory agents that impact cellular and viral gene regulation. This review investigates the multifaceted functions of EBV miRNAs in the pathogenesis of Burkitt lymphoma. EBV miRNAs regulate several cellular processes that are essential for BL development, such as apoptosis, immune evasion, and cellular proliferation. These small, non-coding RNAs target both viral and host mRNAs, finely adjusting the cellular environment to favor oncogenesis. Prominent miRNAs, such as BART (BamHI-A rightward transcript) and BHRF1 (BamHI fragment H rightward open reading frame 1), are emphasized for their roles in tumor growth and immune regulation. For example, BART miRNAs prevent apoptosis by suppressing pro-apoptotic proteins, whereas BHRF1 miRNAs promote viral latency and immunological evasion. Understanding the intricate connections among EBV miRNAs and their targets illuminates BL pathogenesis and suggests novel treatment approaches. Targeting EBV miRNAs or their specific pathways offers a feasible option for developing innovative therapies that aim to disrupt the carcinogenic processes initiated by these viral components. future studies should focus on precisely mapping miRNA‒target networks and developing miRNA-based diagnostic and therapeutic tools. This comprehensive article highlights the importance of EBV miRNAs in Burkitt lymphoma, indicating their potential as biomarkers and targets for innovative treatment strategies.
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2026-07-30 | Malaria and cancer: common features and interactions.
Malaria and cancer are major global health burdens, causing high mortality. While often considered distinct, the two conditions share common features, including continuous cell replication within the body, systemic inflammation, immune modulation and evasion, metabolic reprogramming, endothelial dysfunction, and drug efflux mechanisms. Interestingly, whereas malaria parasite infection promotes Burkitt lymphoma, recent studies in animal models indicate that malaria may activate immune mechanisms against various tumors, thereby improving survival rates. The malaria protein VAR2CSA specifically binds to chondroitin sulfate A in the placenta and metastatic cancer cells, which can be exploited for cancer detection and treatment. Studying the common and unique features of malaria and cancer may facilitate the development of treatment strategies for both diseases.
2026-04-25 | Beyond the Usual Suspects: Emerging Associations Between Epstein-Barr Virus Infection/Infectious Mononucleosis and Cancers.
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus and a causal factor for Burkitt Lymphoma (BL), Hodgkin Lymphoma (HL), gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). Whether EBV contributes to a wider spectrum of cancers remains uncertain. We reviewed MEDLINE, Embase and Web of Science on 30th July 2024 to identify observational studies that examined the association between EBV infection or EBV-infectious mononucleosis (IM) and cancers beyond BL, HL, GC and NPC. Evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. For cancers meeting minimum thresholds we assessed etiologic fractions (EFs), biological plausibility, epidemiological burden, latency after IM, and predictive biomarkers. Thirty-three eligible studies were identified, yielding 13 hypotheses (i.e., specific potential reported associations between EBV infection or IM and individual cancer types) that advanced through GRADE. Breast cancer and NHL had the greatest weight of biological plausibility, cervical and prostate the least. Despite an array of tests, testicular cancer studies provided limited evidence. EFs ranged between 12.3% (IM-breast) and 85.1% (EBV infection-NHL). Breast and prostate cancers had the highest global incidence. Only one study (for NHL) provided data on time from IM to cancer onset, and prostate-specific antigen was the only biomarker identified. In this review, we highlight eight cancers across six cancer groups (breast, cervical, leukaemia/other haematologic, NHL, prostate, testicular) with some evidence of EBV involvement. These results reinforce the potential long-term value of EBV vaccine development, while emphasising the need for high-quality prospective studies with robust methods of viral detection to establish causality.
2025-12-25 | Dissecting Epstein-Barr Virus Dependence Across Diverse Infected Cell Models.
Epstein-Barr virus (EBV) is maintained clonally in a wide array of tumors and cells of lymphoproliferative disorders, yet the degree to which these infected cells continuously depend on EBV remains unresolved. To directly assess EBV dependence, we used two complementary Cas9-based viral eviction strategies: 1) targeting EBNA1 to promote episome dilution during cell division, and 2) targeting repetitive viral genomic regions to rapidly degrade EBV episomes. Using these approaches, we evaluated EBV-loss sensitivity across newly-derived, phenotypically diverse EBV-positive Burkitt lymphoma lines. We also evaluated cell lines from patients with EBV-associated T/NK and epithelial malignancies. We included the Burkitt Lymphoma cell line, Akata-GFP, as our EBV-loss-tolerant control and a lymphoblastoid cell line as our EBV-loss-sensitive control. We observed EBV-loss sensitivity in all the EBV-positive Burkitt Lymphoma cell lines and the chronic active EBV disease cell line. In contrast, the EBV-positive gastric adenocarcinoma lines were markedly less sensitive to EBV loss. EBV latency type did not predict EBV dependence, indicating that viral gene expression programs alone do not dictate reliance on the virus. These findings demonstrate that EBV dependence is prevalent across multiple EBV-associated disease models and is especially pronounced in early-state or newly derived lymphoid malignancies.
2025-12-01 | Abstract 60: Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa
Abstract Purpose: Epstein Barr virus (EBV) is a viral carcinogen associated with Burkitt lymphoma (BL), an aggressive lymphoma that is rare in the U.S. but responsible for most childhood cancer in the equatorial regions of sub-Saharan Africa. EBV is also associated with other cancers, including nasopharyngeal carcinoma in south Asia, some types of gastric cancer, and Hodgkin lymphoma, which contribute to about 2% of the global cancer burden. Discovery of antibody profiles associated with BL would provide new ways to investigate the biology of EBV-associated malignancies, design of screening or diagnostic assays, or develop targeted approaches for treatment. Here, we used an EBV proteome-wide assessment of seroprofiles against EBV in well-characterized cases and controls in the EMBLEM study. Methods: We measured antibody responses against a panel of 199 EBV recombinant proteins expressed from 5 EBV strains (48.2% ag876, 19.1% b958, 18.6% mutu, 9.6% akata, and raji 4.5%) in 701 BL cases and 700 age-, sex-, and area-frequency matched community controls from six regions Kenya, Tanzania, and Uganda. EBV peptide reactivity (standardized signal intensity, SSI) and positivity (number of positive peptides as defined as SSI ≥1) in cases and controls were compared via student’s unpaired t-tests and chi-squared test. Odds ratios of association and 95% confidence intervals were generated by logistic regression models, controlling for sex, country of origin, and by age group. Statistical significance was based on Bonferroni adjusted p-values. Results: Overall, BL cases were more likely to have higher mean (SD) peptide reactivity [case: 209.0 (25.5); control:198.1 (24.0); SSI, p=3.8e-16] and mean (SD) number of seropositive EBV peptides [case:95.9 (35.8); control: 83.0 (34.2); p=7.7e-12] as compared to controls. Total reactivity and seropositivity of peptides from all strains was significantly higher in cases as compared to controls, except for the Akata strain. We identified 66 peptides with mean values significantly higher in BL cases than controls after Bonferroni correction (range of ORs:1.53–4.07), of which 53 showed a significant trend (range of ORs: 1.27–2.28). These EBV peptides were mostly in the late lytic and latent stages of infection. Conclusion: Our results suggest that EBV peptides involved in both latency and lytic replication may influence BL pathogenesis, making them suitable targets for BL prevention and control. Citation Format: Jacquelyn R. Bedsaul-Fryer, Carla Proietti, Martin D. Ogwang, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert K. Tenge, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Hadijah Nabalende, Herry Dhudha, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Hyokyoung G. Hong, Denise Doolan, Sam M. Mbulaiteye. Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 60.
2025-10-29 | Finding the Sweet Spot for the Treatment of B Cell Malignancies.
The glycan profile of cells comprises a high variety of sugar moieties that are attached to proteins (glycoproteins) and lipids (glycolipids) via a process called 'glycosylation'. Cancer cells commonly carry aberrant glycans, which may be of interest for cancer diagnosis, prognosis, as well as the development of novel therapeutic strategies. This review focuses on the differential glycosylation patterns on malignant B cells, including both B cell lymphoma and leukemia. Well-known aberrant glycan profiles on malignant B cells include acquired high mannose N-glycans in the B cell receptor (BCR) of follicular lymphoma (FL), and increased expression of the glycosphingolipid Gb3/CD77 on Burkitt's lymphoma (BL). These structures can be exploited for therapy by using lectins that specifically recognize these patterns with intrinsic cytotoxic activity or in a drug-conjugate format. Furthermore, immunotherapy can be improved by modulating glycans, especially sialic acids. Targeting glycans for immunotherapy is also of interest for chimeric antigen receptor (CAR) T cell therapy, a relatively novel therapy that has been quite effective in various B cell malignancies. Thus, the glycan profile of malignant B cells harbors many opportunities for therapeutic targeting. It is anticipated that further in-depth glycan profiling will open up many more opportunities for the treatment of B cell malignancies.
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Drug Discovery Landscape
4 orphan drug designations for Burkitt lymphoma.
4 orphan drug designations for Burkitt lymphoma.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Sepantronium Bromide | small molecules | FDA | Cothera Bioscience, Inc. | |
CD20-CD47 bispecific fusion protein | proteins | FDA | — | Conjupro Biotherapeutics, Inc. |
Devimistat | small molecules | EMA | IQVIA RDS Ireland Limited | |
6,8-bis(benzylthio)octanoic acid | small molecules | FDA | Cornerstone Pharmaceuticals, Inc. |
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