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
2,488 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:
2,488 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:
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.
2026-07-31 | CHAF1A identified as a candidate biomarker and potential therapeutic target in Burkitt lymphoma through integrated bioinformatics and histopathological analysis.
Burkitt lymphoma (BL) is a highly aggressive malignancy with limited effective treatments due to toxicity/resistance. Identifying and prioritizing candidate biomarkers and potential therapeutic targets from complex transcriptomic data, ahead of functional validation, remains a major unmet need. We integrated differential gene expression analysis across BL vs. control cohorts (Gene Expression Omnibus [GEO] datasets GSE43677/GSE12453) with Random Forest machine learning to prioritize candidates. Validated top genes via immunohistochemistry in an independent cohort (n = 10 BL, n = 10 reactive lymphoid hyperplasia [RLH] controls), followed by immune cell infiltration analysis. This approach identified four candidate genes; only Chromatin Assembly Factor 1 Subunit A (CHAF1A) showed profound protein-level overexpression in BL tumors vs. RLH. In a single-dataset CIBERSORT analysis, CHAF1A expression showed exploratory correlational associations with several immune-cell fractions, most strongly a positive association with M0 macrophages; these in silico associations are hypothesis-generating and do not by themselves establish a mechanistic role in the tumor immune microenvironment. CHAF1A is identified as a candidate biomarker associated with BL that, in exploratory single-dataset analysis, also correlates with immune-cell infiltration; these findings nominate it as a potential therapeutic target that warrants functional validation in future studies.
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.
2026-07-25 | RRx-001 induces apoptosis through reactive oxygen species and endoplasmic reticulum stress in Burkitt lymphoma cells by acting as CD47 and c-Myc regulator.
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma with a poor prognosis in refractory and recurrent patients. RRx-001 is a promising anticancer agent currently under investigation in hematological malignancies; however, its therapeutic effects on BL are not clear. In this study, RRx-001 was found to inhibit the proliferation of BL cells and induce a DNA damage response. RRx-001 can induce apoptosis through caspase cascades with increasing cleavage of Caspases 8, 9, and 3. RRx-001 can also upregulate the expression of DR4, DR5, Bax, and cytochrome C and decrease the expression of Bcl-2, Mcl-1, and XIAP. RRx-001 promotes the accumulation of reactive oxygen species and triggers endoplasmic reticulum (ER) stress in BL cells, both these alterations contribute to RRx-001-induced apoptosis. Additionally, RRx-001 regulates MAPK pathways, and JNK/p38 MAPK signaling functions as a critical hub linking ER stress and oxidative DNA damage. Importantly, RRx-001 also functions as a regulator of CD47 and c-Myc, strongly inhibiting them both in vitro and in a BL cell tumor-bearing mouse model. The overexpression of CD47 increases the proliferation and partially inhibits the apoptosis of BL cells induced by RRx-001. Hence, the findings of this study provided new evidence that RRx-001 may serve as a therapeutic drug for treating BL.
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.
2026-07-31 | CHAF1A identified as a candidate biomarker and potential therapeutic target in Burkitt lymphoma through integrated bioinformatics and histopathological analysis.
Burkitt lymphoma (BL) is a highly aggressive malignancy with limited effective treatments due to toxicity/resistance. Identifying and prioritizing candidate biomarkers and potential therapeutic targets from complex transcriptomic data, ahead of functional validation, remains a major unmet need. We integrated differential gene expression analysis across BL vs. control cohorts (Gene Expression Omnibus [GEO] datasets GSE43677/GSE12453) with Random Forest machine learning to prioritize candidates. Validated top genes via immunohistochemistry in an independent cohort (n = 10 BL, n = 10 reactive lymphoid hyperplasia [RLH] controls), followed by immune cell infiltration analysis. This approach identified four candidate genes; only Chromatin Assembly Factor 1 Subunit A (CHAF1A) showed profound protein-level overexpression in BL tumors vs. RLH. In a single-dataset CIBERSORT analysis, CHAF1A expression showed exploratory correlational associations with several immune-cell fractions, most strongly a positive association with M0 macrophages; these in silico associations are hypothesis-generating and do not by themselves establish a mechanistic role in the tumor immune microenvironment. CHAF1A is identified as a candidate biomarker associated with BL that, in exploratory single-dataset analysis, also correlates with immune-cell infiltration; these findings nominate it as a potential therapeutic target that warrants functional validation in future studies.
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.
2026-07-25 | RRx-001 induces apoptosis through reactive oxygen species and endoplasmic reticulum stress in Burkitt lymphoma cells by acting as CD47 and c-Myc regulator.
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma with a poor prognosis in refractory and recurrent patients. RRx-001 is a promising anticancer agent currently under investigation in hematological malignancies; however, its therapeutic effects on BL are not clear. In this study, RRx-001 was found to inhibit the proliferation of BL cells and induce a DNA damage response. RRx-001 can induce apoptosis through caspase cascades with increasing cleavage of Caspases 8, 9, and 3. RRx-001 can also upregulate the expression of DR4, DR5, Bax, and cytochrome C and decrease the expression of Bcl-2, Mcl-1, and XIAP. RRx-001 promotes the accumulation of reactive oxygen species and triggers endoplasmic reticulum (ER) stress in BL cells, both these alterations contribute to RRx-001-induced apoptosis. Additionally, RRx-001 regulates MAPK pathways, and JNK/p38 MAPK signaling functions as a critical hub linking ER stress and oxidative DNA damage. Importantly, RRx-001 also functions as a regulator of CD47 and c-Myc, strongly inhibiting them both in vitro and in a BL cell tumor-bearing mouse model. The overexpression of CD47 increases the proliferation and partially inhibits the apoptosis of BL cells induced by RRx-001. Hence, the findings of this study provided new evidence that RRx-001 may serve as a therapeutic drug for treating BL.
Access all drug discovery papers and probability of success in trials forecasts:
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Drug Discovery Landscape
4 orphan drug designations for Burkitt lymphoma.
4 orphan drug designations for Burkitt lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Sepantronium Bromide | small molecules | FDA | 2023-12-07 | — | Cothera Bioscience, Inc. |
CD20-CD47 bispecific fusion protein | proteins | FDA | 2022-06-08 | — | Conjupro Biotherapeutics, Inc. |
Devimistat | small molecules | EMA | 2021-10-15 | — | IQVIA RDS Ireland Limited |
6,8-bis(benzylthio)octanoic acid | small molecules | FDA | 2018-01-25 | — | Cornerstone Pharmaceuticals, Inc. |
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