2026-07-08 | Hairy cell leukemia in a 51-year-old Syrian male: a case report.
Hairy cell leukemia (HCL), a rare B-cell lymphoproliferative disorder, originates from the splenic marginal zone B cell. However, diagnosis can be particularly challenging in resource-limited settings where advanced tests are not readily available. Misclassification may result in non-selective chemotherapy exposure and increased toxicity. Reporting such cases is important to highlight diagnostic challenges in resource-limited countries. A 51-year-old male presented with abdominal discomfort, weight loss, and fatigue. Examination revealed splenomegaly. Initial evaluation suggested lymphoplasmacytic lymphoma, and the patient received multi-agent chemotherapy (R-CHOP), which was complicated by severe cytopenias. Splenectomy was performed, yielding a spleen weighing 2216 g. Histopathology and immunophenotyping confirmed hairy cell leukemia. Molecular testing for BRAF V600E (the gold standard for diagnosis) was unavailable due to financial and infrastructural restrictions. Treatment was switched to single-agent cladribine, resulting in marked clinical improvement and a significant reduction in chemotherapy adverse effects. Follow-up imaging and blood work revealed that the patient was in complete remission. In our case, we emphasize the diagnostic challenges of HCL in low-resource environments and clarify how the empirical administration of R-CHOP chemotherapy led to unnecessary toxicity and suboptimal outcomes. Splenectomy played a crucial diagnostic role when bone marrow tests were directional but not conclusive. We provide an extensive review of differential diagnoses, immunophenotypic hallmarks, what lies beyond the BRAF V600E mutation, and therapeutic approaches. Early recognition of HCL is crucial to avoid delayed optimal therapy and to enhance patient outcomes. This case emphasizes the critical role of morphology and immunophenotyping in confirming HCL, especially in resource-limited countries.
Open article ↗
2026-06-12 | Real-world treatment and outcomes in hairy cell leukemia: a multicenter retrospective cohort including BRAF inhibitor therapy.
Hairy cell leukemia (HCL) is a rare B-cell malignancy traditionally treated with purine analogue-based regimens. Although BRAF inhibitors are established in relapsed or refractory disease, their role as first-line therapy remains incompletely defined. We conducted a multicenter retrospective study evaluating real-world treatment of adults with classic HCL. A total of 110 patients were included. First-line therapies were cladribine (64%), cladribine plus rituximab (11%), rituximab (9%), and vemurafenib-based regimens (9%). Overall, response rate to first-line therapy was 80% (complete response rate of 65%). Median overall survival was 24.4 years. Patients treated first-line with vemurafenib-based regimens achieved an overall response rate of 80%, similar to purine analogue-based therapy. Hospitalization rates were similar across treatment groups. Vemurafenib-based therapy and rituximab monotherapy were preferentially used in older patients with greater baseline anemia. This study provides early insight into BRAF inhibitor use in HCL, highlighting encouraging responses in a limited number of patients.
Open article ↗
2026-05-27 | DUSP1 is a Key Driver of Disease Persistence and Potential Therapeutic Target in Hairy Cell Leukemia.
Classic hairy cell leukemia (HCL) is a rare indolent B cell lymphoproliferative disorder characterized by the driver mutation BRAF V600E. Standard treatment with purine analogs (i.e. cladribine) induces long-term remissions, but up to 25% of patients relapse early. Even when targeting BRAF V600E, residual HCL cells frequently persist in the bone marrow (BM). To unravel additional biologic alterations contributing to HCL disease persistence, we performed single-cell RNA sequencing in sorted primary HCL cells from long-term versus short-term cladribine responders (LT-R versus ST-R: >10 versus ≤3 years PFS) at diagnosis and in ST-R at diagnosis versus relapses. We identified a distinct HCL subcluster characterized by elevated DUSP1, FOS, and JUND expression, which was detected in all patients and persisted or even expanded at relapses. Cancer pathway analysis suggested enhanced tumor microenvironment dependency as reflected by suppression of the p38-MAP kinase pathway. In the absence of a suitable BRAF V600E-mutated HCL cell line, we validated HAIR-M cells (BRAF D594E) as a bona fide experimental HCL model. The activating BRAF D594E mutation mimics V600E-induced downstream signals that can efficiently be targeted by BRAF inhibitors (BRAFi). HAIR-M co-culture with BM stromal cells (BMSC) strongly induced DUSP1 that was accompanied by protection from BRAFi-induced HAIR-M apoptosis. The functional importance of DUSP1 was corroborated by demonstrating that BMSC-induced protection from cell death could be overcome through DUSP1 inhibition. Our results might set the stage for future clinical testing of DUSP1 inhibition to eliminate minimal residual disease (MRD) and prevent disease relapse in HCL.
Open article ↗
