2026-08-11 | First Philippine report of myeloproliferative neoplasms with concurrent JAK2 and BCR::ABL1 mutations.

Myeloproliferative neoplasms (MPNs) are broadly classified into BCR::ABL1-positive chronic myeloid leukaemia (CML) and BCR::ABL1-negative subtypes such as polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis. Although traditionally considered mutually exclusive, rare cases of coexisting BCR::ABL1 rearrangement and Janus kinase 2 (JAK2) mutation have increasingly been recognised.We report the first Philippine case series of three patients with concurrent CML and JAK2-positive MPNs. Two patients developed PV 6-9 years after the initial diagnosis of CML despite ongoing tyrosine kinase inhibitor (TKI) therapy and molecular response, while a third patient had persistent thrombocytosis and was later found to have a concomitant JAK2-mutated MPN with fibrotic marrow features after 4 years.Compared with previously reported cases, our series demonstrates similarly delayed emergence of JAK2-mutated clones while highlighting real-world challenges in TKI intolerance, sequential TKI use and the need for combined cytoreductive strategies in a resource-limited setting.

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2026-08-09 | The thrombopoietin receptor in myeloproliferative neoplasms: A unifying mechanism of disease pathogenesis and therapeutic targeting.

The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are clonal hematopoietic stem cell disorders unified by constitutive thrombopoietin receptor (MPL) signaling. All 3 MPN driver mutations, JAK2, CALR, and MPL, converge on enhanced MPL signaling, establishing the thrombopoietin (TPO)/MPL axis as the central molecular hub linking clonal hematopoiesis to the cardinal manifestations of MPN, including thrombosis, hemorrhage, and fibrotic progression. As the principal regulator of hematopoietic stem cell maintenance and megakaryopoiesis and a key mediator of platelet priming, the TPO/MPL axis links stem cell biology to thromboinflammation and disease progression. This review summarizes the physiologic functions of the TPO/MPL axis, its dysregulation in MPN, and the downstream mechanisms linking aberrant MPL signaling to thrombosis, hemorrhage, and fibrotic progression. We further highlight recent advances in our understanding of TPO/MPL signaling in platelet biology, including its roles in platelet activation, metabolism, and thromboinflammation, and discuss emerging therapeutic strategies targeting the TPO/MPL pathway with the goal of simultaneously reducing thrombohemorrhagic complications, limiting fibrotic progression, and diminishing the malignant stem cell clone.

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2026-08-08 | Case Report: Polycythemia vera presenting as persistent unexplained low-grade fever.

Persistent fever as an initial manifestation of polycythemia vera (PV) is uncommon and may lead to diagnostic delay. We report a 72-year-old woman with recurrent low-grade fever for 1 month, with a maximum temperature not exceeding 38.0 °C. Although this presentation did not meet the classic fever-of-unknown-origin temperature threshold, it prompted an FUO-like diagnostic evaluation because routine infectious and autoimmune investigations were unrevealing and empirical antimicrobial therapy was ineffective. Laboratory evaluation revealed elevated hemoglobin and hematocrit levels, accompanied by leukocytosis and initially high-normal platelet counts that later progressed to thrombocytosis. Chest CT/PET-CT showed diffuse ground-glass/interstitial pulmonary changes; active bacterial pneumonia was considered unlikely based on the absence of respiratory symptoms, procalcitonin at the upper limit of the normal range, negative cultures and sputum smears, and absence of FDG-avid pulmonary consolidation, although a concomitant viral or noninfectious inflammatory pulmonary process could not be completely excluded. Bone marrow biopsy showed hypercellular marrow with panmyelosis and megakaryocytic proliferation, and molecular testing identified a JAK2 V617F mutation with a high allele burden. The diagnosis of PV was established based on the 5th edition of the World Health Organization (WHO) diagnostic criteria. The patient was treated with hydroxyurea and aspirin, resulting in gradual resolution of fever and improvement in hematological parameters. This case highlights that PV should be considered in the differential diagnosis of persistent unexplained low-grade fever when erythrocytosis and other myeloproliferative features are present, while alternative pulmonary causes should be assessed carefully.

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2026-08-07 | Ropeginterferon alfa-2b in Polycythemia Vera: A systematic review and meta-analysis.

Ropeginterferon alfa-2b, a novel monopegylated interferon with improved pharmacokinetics, has emerged as a promising cytoreductive agent for managing polycythemia vera (PV). Despite increasing adoption, evidence synthesis of its efficacy and safety compared to standard care remains limited. The manuscript aimed to evaluate the efficacy of ropeginterferon alfa-2b in comparison to standard treatment options, including hydroxyurea and phlebotomy, in achieving complete hematologic response, partial molecular response (PMR), and reducing JAK2V617F allele burden in patients with PV. A systematic search of 4 databases was conducted up to April 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing ropeginterferon alfa-2b with standard therapies in PV patients were included. Meta-analyses were performed using random-effects models to derive odds ratios for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Sensitivity and subgroup analyses were conducted, and risk of bias was assessed using RoB 2.0. Three RCTs comprising 522 patients were analyzed. Ropeginterferon alfa-2b showed no statistically significant advantage overall or over hydroxyurea for complete hematological response (CHR), PMR, or JAK2 allele burden reduction. However, subgroup analyses revealed significant benefits over phlebotomy alone in all 3 outcomes: CHR (odds ratio [OR] 3.05; 95% confidence interval [CI]: 1.36-6.80; P = .007), PMR (OR 36.34; 95% CI: 2.11-625.93; P = .01), and allele burden reduction (MD -13.70; 95% CI: -19.24 to -8.16; P < .00001). Ropeginterferon alfa-2b demonstrates no statistically significant difference compared to hydroxyurea, but gives better outcomes over phlebotomy in short-term efficacy for PV management. Its favorable molecular and hematologic outcomes support its role as a disease-modifying therapy, particularly in low-risk patients. However, larger and longer-term trials are needed to confirm these benefits across broader populations.

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2026-08-04 | Acute erythroid leukaemia transformation in polycythaemia vera with leukemic involvement in liver and ascites.

Polycythaemia vera (PV) may rarely evolve into acute erythroid leukaemia (AEL). We herein report a known case of JAK2 p. V617F mutated PV presenting with progressive hepatosplenomegaly, abdominothoracic lymphadenopathy, ascites and various haematological derangements. Rapid diagnostic work-up revealed extensive marrow, hepatic and ascitic fluid infiltration by many CD71+, LMO2+ and p53+ proerythroblasts. Next generation sequencing showed TP53, ASXL1 and TET2 gene mutations. A chemotherapeutic regimen of ruxolitinib, azacitidine and venetoclax was initiated. A comprehensive review of the English literature emphasises clinical, morphologic, immunophenotypic and genetic characteristics of AEL transformation in PV.

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