bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–11–15
seventeen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Predictive factors for TKI discontinuation eligibility and treatment-free remission in chronic myeloid leukemia.
  2. The new Iron Age in polycythemia vera.
  3. Is Circulating Tumor DNA Ready for Clinical Use in Large B-cell Lymphoma?
  4. Sustained measurable residual disease negativity or guaranteed survival time in multiple myeloma?
  5. Pharmacological SOS1 inhibitor BI-3406 synergizes with BCR::ABL1 TKIs reducing leukemia stem cells and overcoming imatinib resistance in CML.
  6. Orelabrutinib plus R-CHOP in patients with newly diagnosed non-GCB double-expressor DLBCL: A single-arm, phase II study.
  7. Idiopathic Multicentric Castleman Disease Unresponsive to One IL-6 Inhibitor May Respond to Another IL-6 Inhibitor.
  8. Is There an Association Between GLP-1RA Use and Blood Cancer Incidence or Progression?
  9. Distinct asciminib sensitivity profiles between BCR::ABL1 p190 and p210 isoforms.
  10. Is Bone Marrow Examination Still Required at Diagnosis of Typical Chronic-Phase Chronic Myeloid Leukemia? Evidence From Paired Peripheral Blood and Bone Marrow Cytogenetics.
  11. Dasatinib Dose Optimization With Weekend Drug Holiday for Improved Tolerability in Chronic Myeloid Leukemia (DasaHIT): A German Chronic Myeloid Leukemia Alliance Randomized Trial.
  12. Fit for the fight: BTK inhibitors prime CAR T cells in CLL.
  13. Stage 0 hematogones essentially lack CD9 expression: comparative immunophenotypic analysis of hematogone subsets and myeloid blasts.
  14. Monoclonal Gammopathy of Neurologic Significance: A Practical Framework for Diagnosis and Management.
  15. Preclinical characterization of the potent and selective MALT1 inhibitor safimaltib in B-cell lymphoma models.
  16. How I diagnose myeloid or lymphoid neoplasms with tyrosine kinase gene fusions.
  17. Use of RBC Parameters to Establish Functional Ferritin Cutoffs for the Potential Diagnosis of Iron Deficiency in Adults and Children.
  1. Int J Hematol. 2026 Nov 11.
    Predictive factors for TKI discontinuation eligibility and treatment-free remission in chronic myeloid leukemia.
    Takaaki Ono.
      Treatment-free remission (TFR) is an important therapeutic goal in chronic-phase chronic myeloid leukemia. However, not all patients achieve tyrosine kinase inhibitor (TKI) discontinuation eligibility (TDE), and approximately half of those who discontinue therapy experience molecular recurrence. Thus, achieving TDE and maintaining TFR represent related but distinct clinical challenges. Early molecular response kinetics, treatment duration, depth and stability of response, prior TKI resistance, and BCR::ABL1 transcript type have been associated with these outcomes. Emerging biomarkers, including highly sensitive methods, leukemic stem cell characteristics, clonal hematopoiesis, immune-cell profiles, inflammatory cytokines, and host immunogenetic factors, may further refine prediction. Transcriptomic studies, artificial intelligence-based analysis, and mathematical modeling also offer promising approaches for integrating disease biology, host immunity, and treatment dynamics. Whether predictors identified with conventional TKIs apply to asciminib requires further evaluation. Future strategies should integrate longitudinal molecular and biological information to enable safer and appropriately timed TKI discontinuation.
    Keywords:  Chronic myeloid leukemia; Treatment-free remission; Tyrosine kinase inhibitor discontinuation
    DOI:  https://doi.org/10.1007/s12185-026-04303-1
  2. Blood. 2026 Nov 12. 148(20): 2439-2441
    The new Iron Age in polycythemia vera.
    David M Ross.
      
    DOI:  https://doi.org/10.1182/blood.2026036007
  3. Blood. 2026 Nov 10. pii: blood.2026033073. [Epub ahead of print]
    Is Circulating Tumor DNA Ready for Clinical Use in Large B-cell Lymphoma?
    Reid W Merryman, Mark Roschewski.
      Response assessment after frontline therapy for large B-cell lymphoma risk-stratifies patients into those at low risk for relapse and those with residual disease. Positron emission tomography scans form the cornerstone of the response criteria but cannot detect molecular-only disease. Circulating tumor DNA detects measurable residual disease (MRD) after therapy which is emerging as an adjunct tool for complex clinical decision-making. We discuss how MRD after therapy can be clinically implemented and additional data needed to unlock its full potential.
    DOI:  https://doi.org/10.1182/blood.2026033073
  4. Br J Haematol. 2026 Nov 08.
    Sustained measurable residual disease negativity or guaranteed survival time in multiple myeloma?
    Xin Zhou, Ningning Shan.
      
    DOI:  https://doi.org/10.1111/bjh.70949
  5. Cell Death Dis. 2026 Aug 12. pii: 951. [Epub ahead of print]17(1):
    Pharmacological SOS1 inhibitor BI-3406 synergizes with BCR::ABL1 TKIs reducing leukemia stem cells and overcoming imatinib resistance in CML.
    Rósula García-Navas, Carmela Gómez, Anabel Clemente-Serrano, Belén Zamora-Valdivieso, Sara Pérez-Gutiérrez, Andrea Olarte-San Juan, Alba Díaz-Aguilera, Sonsoles Calvo-Jimenez, Nuria Calzada, Alberto Fernández-Medarde, Magdalena Sierra, Fermín Sánchez-Guijo, Dolors Colomer, Robyn L Schenk, Marco H Hofmann, Kaja Kostyrko, Eugenio Santos.
      Disease persistence and resistance remain major challenges in chronic myeloid leukemia (CML). We evaluated pharmacological SOS1 inhibition with BI-3406, alone or in combination with BCR::ABL1 tyrosine-kinase inhibitors (TKI), across complementary preclinical models. In p210BCR/ABL transgenic mice, BI-3406 plus imatinib was well-tolerated, markedly prolonged survival, improved hematologic indices, reduced splenomegaly, and decreased bone-marrow LSK/hematopoietic stem and progenitor cells compared to either agent alone. In human CML cell lines and primary patient-derived bone-marrow cells, combined therapeutic treatments with BI-3406 and imatinib (standard of care BCR-ABL TKI) or next-generation TKIs showed strong synergistic suppression of cellular proliferation and increased apoptosis relative to single-agent treatment. Remarkably, drug combinations containing BI-3406 also restored TKI sensitivity to primary bone-marrow cell samples derived from a variety of CML patients that had been initially identified as clinically resistant to imatinib. Mechanistically, BI-3406 attenuated RAS/RAC-ERK/AKT signaling, while SOS1 knockdown phenocopied BI-3406-mediated imatinib sensitization, supporting an on-target SOS1-dependent therapeutic effect. Upregulation of the membrane transport protein SLC22A4 following combination treatment may contribute to the rescued TKI sensitivity but is probably not the sole underlying mechanism as BI-3406+imatinib retained strong synergistic activity despite SLC22A4 knockdown. Comparison of the transcriptomic profiles revealed that the combined BI-3406+imatinib drug regimen triggered the strongest repression of oncogenic, metabolic and stemness-associated transcriptional programs in treated CML cells. Consistently, serial replating MethoCult assays functionally confirmed the impairment of clonogenic self-renewal capacity and the depletion of murine LSK and human Lin⁻CD34⁺CD38⁻ stem/progenitor-enriched compartments after dual SOS1 and BCR::ABL1 inhibition. Our data support SOS1 targeting as a rational therapeutic strategy to potentiate TKI efficacy, impair CML stem/progenitor self-renewal, and restore drug responsiveness in clinically relevant TKI-resistant settings.
    DOI:  https://doi.org/10.1038/s41419-026-09170-6
  6. Br J Haematol. 2026 Nov 10.
    Orelabrutinib plus R-CHOP in patients with newly diagnosed non-GCB double-expressor DLBCL: A single-arm, phase II study.
    Yang Yang, Yi Zhao, Wenjun Wu, Gaofeng Zheng, Donghua He, Li Yang, Yi Li, Fuming Zi, Fengping Zhou, Cai Wu, Jingsong He, Zhen Cai.
      Double-expressor diffuse large B-cell lymphoma (DE-DLBCL) patients, defined by co-expression of MYC proto-oncogene protein (≥40%) and B-cell lymphoma 2 protein (≥50%), typically have poor outcomes with the traditional first-line R-CHOP regimen. We conducted a multicentre, single-arm, phase II study to evaluate the efficacy and safety of first-line orelabrutinib plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), designated O-RCHOP, in patients with non-germinal centre B-cell-like (non-GCB) DE-DLBCL. From 19 November 2021 to 6 February 2025, 49 patients were enrolled. With a median follow-up of 26.6 months, median event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) were not reached, and the estimated 2-year EFS, PFS and OS rates were 82.0% (95% confidence intervals [CIs]: 71.2%-94.3%), 82.0% (95% CI: 71.2%-94.3%) and 97.9% (95% CI: 94.0%-100.0%) respectively. At the end of treatment, the complete response rate was 89.8% (44/49; 95% CI: 77.8%-96.6%), and the objective response rate was 95.9% (47/49; 95% CI: 86.0%-99.5%). Grade ≥3 adverse events (AEs) occurred in 51.0% of patients, with neutropenia (38.8%) being the most common. No patients died because of AEs. Genetic alteration profiling revealed that the frequently mutated genes were Pim-1 proto-oncogene, serine/threonine kinase (PIM1; 63.6%), MYD88 innate immune signal transduction adaptor (MYD88; (51.5%) and CD79b molecule (CD79B; 48.5%). O-RCHOP achieved encouraging efficacy with a manageable safety profile in newly diagnosed DE-DLBCL, supporting its feasibility as a first-line regimen.
    Keywords:  O‐RCHOP; R‐CHOP; double‐expressor DLBCL; first‐line; orelabrutinib; phase II study
    DOI:  https://doi.org/10.1111/bjh.70944
  7. Blood Adv. 2026 Nov 10. pii: bloodadvances.2026020893. [Epub ahead of print]
    Idiopathic Multicentric Castleman Disease Unresponsive to One IL-6 Inhibitor May Respond to Another IL-6 Inhibitor.
    Kayla McHugh, Yuan Huang, Bridget Austin, Larissa Borys, Abiola H Irvine, Daisy V Alapat, Adam Bagg, Amy Chadburn, Mary Jo Lechowicz, Megan S Lim, Gordan Srkalovic, Frits van Rhee, David C Fajgenbaum, Lu Zhang, Joshua D Brandstadter.
      Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder defined by lymphadenopathy with distinctive histopathology and systemic inflammation that can progress to multiorgan failure. Siltuximab, a monoclonal antibody targeting the interleukin-6 (IL-6) cytokine, is the only FDA-approved treatment for iMCD and is considered first-line therapy. Tocilizumab, an IL-6 receptor antagonist, approved for iMCD in Japan and used off-label is often viewed as clinically interchangeable with siltuximab due to shared pathway inhibition. Limited treatment alternatives exist for patients whose disease is refractory to IL-6 inhibition. Using two independent iMCD patient registries, we identified patients who received siltuximab and tocilizumab at different periods and had an assessable response to each inhibitor. Eight out of 14 patients who received both therapies were refractory to the first and then responsive to the second IL-6 inhibitor; six patients were refractory to both IL-6 inhibitors. Responses were durable over available follow-up and were accompanied by significant improvements in inflammatory markers and disease severity scores. While a subset of patients may have had improved response to the second IL-6 inhibitor due to shorter treatment durations or the use of other medications, all were refractory after receiving at least three doses of the first IL-6 inhibitor. These findings suggest that there may be different IL-6-related mechanisms across patients and that selected patients who do not respond to an initial IL-6 inhibitor should be considered for a second IL-6 inhibitor.
    DOI:  https://doi.org/10.1182/bloodadvances.2026020893
  8. Am J Hematol. 2026 Nov 13.
    Is There an Association Between GLP-1RA Use and Blood Cancer Incidence or Progression?
    Hagop Kantarjian, Ayalew Tefferi.
      
    Keywords:  GLP‐1 receptor agonists; leukemia; lymphoma; myelodysplastic; myeloma; myeloproliferative
    DOI:  https://doi.org/10.1002/ajh.70552
  9. Exp Hematol Oncol. 2026 Nov 11. pii: 122. [Epub ahead of print]15(1):
    Distinct asciminib sensitivity profiles between BCR::ABL1 p190 and p210 isoforms.
    Elias Lagonik, Luke J Quinlan, Elyse C Page, Daniel P McDougal, Laura N Eadie, John B Bruning, David T Yeung, Timothy P Hughes, Deborah L White.
      BCR::ABL1 is the oncogenic driver of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph + ) acute lymphoblastic leukemia (ALL), with BCR::ABL1 p210 and p190 being the predominant isoforms. Asciminib, an inhibitor that specifically targets the ABL myristate pocket (STAMP), has demonstrated efficacy in both pre-clinical and clinical studies against p210-driven CML, including cases where resistance mediated by ATP-pocket mutations has developed during prior tyrosine kinase inhibitor (TKI) therapy. The resistant mutation profile of asciminib is currently considered largely distinct from that of ATP-competitive TKIs. In our study, we demonstrate that several ATP-pocket mutations, including the V299L, F311I, T315I, and F317C/L, confer high levels of resistance to asciminib in the p190 isoform (> 1000-fold increase in LD50asciminib values compared to non-mutated BCR::ABL1 p190), but remain sensitive when occurring in the p210 isoform. The T315A was the only tested mutation in BCR::ABL1 p190 sensitive to asciminib. Furthermore, cells expressing BCR::ABL1 p190 mutations exhibited decreased kinase inhibition following STAMP treatment, indicative of an active kinase. Analogous results were obtained for MK-4208 (formerly known as TERN-701), a clinically active investigational STAMP compound. In the BCR::ABL1 p190 setting, this work reveals an overlapping resistance profile between STAMP compounds and TKIs, with important considerations for STAMP-based therapy. It challenges two key assumptions: that asciminib dose escalation can overcome resistant ATP-pocket mutations and that targeted therapy sensitivity profiles are equivalent between the p190 and p210 isoforms.
    Keywords:  Asciminib; BCR::ABL1; CML; MK-4208; Ph + ALL; Resistance; STAMP; T315I; TERN-701; p190
    DOI:  https://doi.org/10.1186/s40164-026-00859-0
  10. Am J Hematol. 2026 Nov 11.
    Is Bone Marrow Examination Still Required at Diagnosis of Typical Chronic-Phase Chronic Myeloid Leukemia? Evidence From Paired Peripheral Blood and Bone Marrow Cytogenetics.
    Mohammed Al Kurnas, Muluken Megiso, Ayalew Tefferi, Xi Zhang, Kebede H Begna.
      
    Keywords:  bone marrow; concordance; cytogenetics; diagnosis; peripheral blood
    DOI:  https://doi.org/10.1002/ajh.70555
  11. J Clin Oncol. 2026 Nov 13. JCO2600899
    Dasatinib Dose Optimization With Weekend Drug Holiday for Improved Tolerability in Chronic Myeloid Leukemia (DasaHIT): A German Chronic Myeloid Leukemia Alliance Randomized Trial.
    German CML Study Group
       PURPOSE: To compare standard-dose dasatinib 100 mg once daily with reduced-dose using a weekend drug holiday to improve tolerability for patients with chronic myeloid leukemia (CML).
    PATIENTS AND METHODS: Patients with chronic phase CML (CP-CML) were randomly assigned to either receive standard-of-care dasatinib 100 mg once daily or an intermittent dasatinib schedule (5 days on, 2 days [weekend] off) in a prospective multicenter phase III trial. Achievement of major molecular remission (MMR) at 24 months and a newly developed cumulative toxicity score were coprimary end points.
    RESULTS: Of 289 eligible patients, 147 were assigned to standard-of-care dasatinib and 142 to intermittent dosing. Eighty percent of patients received first-line treatment (n = 232). In the standard arm, 105 of 130 patients (81% [95% CI, 74% to 88%) achieved MMR at 24 months compared with 101 of 130 patients (78% [95% CI, 71% to 85%]) in the experimental arm resulting in noninferiority within the prespecified noninferiority margin of 15% (P = .009). Among second- or later-line patients, MMR at 24 months was 24% lower, failing noninferiority. Comparison of grade 2-4 toxicities revealed no significant difference between the treatment arms. However, a post hoc analysis of toxicities of special interest (pleural effusion/pericardial effusion) showed 21 of 130 patients (16%) in the standard arm versus 10 of 125 (8%) patients in the experimental arm (P = .0464). Consistently, health-related quality of life improved mainly in first-line patients, with more favorable outcomes in the experimental arm.
    CONCLUSION: Intermittent dasatinib dosing with weekend treatment holidays in patients with CP-CML is noninferior to continuous dosing with respect to MMR at 24 months, at least in the first-line setting. The incidence of pleural or pericardial effusion appears to be reduced compared with standard-of-care continuous dosing.
    DOI:  https://doi.org/10.1200/JCO-26-00899
  12. Blood. 2026 Nov 12. 148(20): 2437-2439
    Fit for the fight: BTK inhibitors prime CAR T cells in CLL.
    John G Gribben.
      
    DOI:  https://doi.org/10.1182/blood.2026035633
  13. Am J Clin Pathol. 2026 Nov 04. pii: aqag127. [Epub ahead of print]166(5):
    Stage 0 hematogones essentially lack CD9 expression: comparative immunophenotypic analysis of hematogone subsets and myeloid blasts.
    Jessica Hughes, Joo Song, Huiyan Ma, Winston Lee, Karl Gaal, Parastou Tizro, Yan Liu, Elizabeth Quirk, Lori Soma.
       OBJECTIVES: Measurable residual disease (MRD) assessment of B lymphoblastic leukemia (BLL) by flow cytometry (FC) can be confounded by normal populations, particularly stage 0 hematogones (HGs), following CD19-targeted therapy. Few studies have reported expression patterns or compared them with other populations. We assessed expression of CD9, CD34, CD45, CD58, CD66c/CD13/CD33, and CD81 on stage 0 HGs and compared the findings to stage 1 to 3 HGs and myeloid blasts (MBs).
    METHODS: Cases of BLL MRD FC were reviewed for residual disease, and negative cases with stage 0 HGs were further evaluated for stage 1 to 3 HGs and MBs. Dot plot patterns and median fluorescence intensity (MFI) were evaluated and compared across populations.
    RESULTS: Unlike stage 1 to 3 HGs, stage 0 HGs essentially lacked CD9 expression. CD9 MFI on stage 1 to 3 HGs demonstrated a broad range, typically with prominent bright components, although some cases showed significant CD9-negative subsets. Stage 0 HG CD34 was similar to stage 1 and slightly lower than MBs. CD45 expression was similar among stage 0 HGs, stage 1 HGs, and MBs. Although all HG stages appeared overall similar on dot plots, CD58 and CD66c/CD13/CD33 MFIs were higher, and CD81 MFI was lower in stage 0 HGs than in later stages. CD81 expression was higher in all HG stages compared with MBs.
    CONCLUSIONS: Unlike stage 1 to 3 HGs, stage 0 HGs essentially lack CD9 expression. CD58, CD66c/CD13/CD33, and CD81 may show slight shifts in intensity compared with other stages. These findings should be considered when assessing BLL MRD by FC following CD19-directed therapy.
    Keywords:  BLL; CD13; CD33; CD58; CD66c; CD81; CD9; MRD; flow cytometry; hematogones; stage 0
    DOI:  https://doi.org/10.1093/ajcp/aqag127
  14. JCO Oncol Pract. 2026 Nov 09. OP2600658
    Monoclonal Gammopathy of Neurologic Significance: A Practical Framework for Diagnosis and Management.
    Manisha Bhutani, Martin Porebski, Brandon Tedder, Urvi Desai, Barry Paul.
      Monoclonal gammopathy of neurologic significance (MGNS) refers to peripheral neuropathies that are attributable to a monoclonal immunoglobulin produced by an underlying clonal plasma cell population or B-cell population in the absence of multiple myeloma, amyloid light chain amyloidosis, or polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes syndrome. Because the prevalence of both monoclonal gammopathy of undetermined significance (MGUS) and peripheral neuropathy increases with age, their coexistence is frequently incidental. However, population-based studies demonstrate a significantly higher risk of neuropathy among patients with MGUS compared with matched controls. Establishing causality requires careful clinical phenotyping, correlation with electrodiagnostic studies, and systematic exclusion of alternative and potentially life-threatening causes that require urgent intervention. This review presents a practical, stepwise diagnostic and therapeutic framework for MGNS, emphasizing multidisciplinary collaboration between hematology and neurology. The approach is illustrated through two representative clinical scenarios: IgM MGUS with anti-myelin-associated glycoprotein (anti-MAG) neuropathy and non-IgM MGUS with chronic inflammatory demyelinating polyneuropathy (CIDP) or its variants. Treatment approaches differ fundamentally between these subtypes. B-cell-directed therapy with rituximab is the most commonly used first-line treatment for IgM anti-MAG neuropathy, whereas non-IgM MGNS with CIDP is managed with immunomodulatory strategies including intravenous immunoglobulin, corticosteroids, and plasmapheresis. We also discuss novel therapeutics, including Bruton tyrosine kinase inhibitors and complement-directed therapies. This framework provides clinicians with a structured approach to assess causal likelihood, stratify patients by neuropathy subtype, and guide evidence-based treatment decisions across the MGNS spectrum.
    DOI:  https://doi.org/10.1200/OP-26-00658
  15. Blood Cancer Discov. 2026 Nov 09.
    Preclinical characterization of the potent and selective MALT1 inhibitor safimaltib in B-cell lymphoma models.
    Ulrike Philippar, Lorena Fontan, Min Xia, Nele Vloemans, Mariette Bekkers, Marcello Gaudiano, Onyi Irrechukwu, Diede van den Biggelaar, Tatiana Perova, Irene Guimerans-Lorenzo, Katarzyna Wnuk-Lipinska, Ivo Cornelissen, Marjolein van Heerden, Bas-Jan van der Leede, Katie Amssoms, Rui Xu, Joanna Grant, Emanuele Trella, Yann Abraham, Kristof Kimpe, Bart Medaer, Anthony Greway, Jan Snoeys, Frank Jacobs, Maxwell D Cummings, Weimei Sun, Jan Willem Thuring, Tongfei Wu, Stan Gaj, Bie Verbist, Peter J Connolly, Nigel Austin, Sriram Balasubramanian, Jacqueline Kinyamu-Akunda, Kathryn Packman, James P Edwards, Yusri Elsayed, Nele Fourneau, Franck Morschhauser, John F Gerecitano, Jacqueline Bussolari, Ari M Melnick, Ricardo M Attar.
      Constitutive activation of the B-cell receptor (BCR) pathway drives non-Hodgkin lymphomas. MALT1 is a key mediator of NF-κB signaling downstream of B- and T-cell receptors. Herein, we report development of safimaltib (JNJ-67856633), a selective, allosteric inhibitor of MALT1 protease. The crystal structure of safimaltib bound to MALT1 was determined, and enzyme kinetic studies were performed to characterize its inhibitory mechanism. Sub-micromolar doses of safimaltib inhibited growth of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cell lines with activation of NF-κB signaling and models mimicking BTK inhibition resistance. Notably, activating mutations in BCR-pathway components were strongly associated with safimaltib response in vitro. Safimaltib demonstrated efficacy in DLBCL and MCL mouse models and synergy with a BTK inhibitor. Safimaltib was well tolerated in preclinical immunocompetent animal models with a safety profile supporting MALT1 targeting in humans. Overall, these results provide rationale for the first-in-human MALT1 inhibitor clinical trial.
    DOI:  https://doi.org/10.1158/2643-3230.BCD-26-0182
  16. Am J Clin Pathol. 2026 Nov 04. pii: aqag119. [Epub ahead of print]166(5):
    How I diagnose myeloid or lymphoid neoplasms with tyrosine kinase gene fusions.
    Wei-Ying Jen, Sanam Loghavi.
       OBJECTIVES: Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TKs) are a clinically and genetically heterogeneous group of hematologic malignancies unified by constitutively activating gene fusions involving receptor or nonreceptor tyrosine kinases. Classification systems recognize 6 distinct subtypes defined by rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ABL1. Accurate diagnosis has therapeutic implications, as several subtypes are remarkably sensitive to tyrosine kinase inhibitors (TKIs).
    METHODS: Through illustrative clinical scenarios and integration of current evidence, we provide a practical framework for diagnosing MLN-TKs, with an emphasis on the morphologic triggers, cytogenetic and molecular testing strategies, and diagnostic pitfalls relevant to each subtype. We incorporate recent data from large registry-based cohorts, updated World Health Organization/International Consensus Classification criteria, and consensus proposals from the Classification Advancement Meeting.
    RESULTS: Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions encompass a morphologic spectrum from indolent chronic eosinophilic myeloproliferative neoplasms to acute leukemias and extramedullary blast-phase disease. Eosinophilia, while common, is neither universal nor sufficient for diagnosis; the diagnostic anchor is molecular confirmation of a TK gene fusion. A tiered testing strategy, including conventional karyotype and targeted fluorescence in situ hybridization, followed by reverse transcription polymerase chain reaction, RNA sequencing, or optical genome mapping when first-line testing is negative, maximizes diagnostic yield. Demonstration of mature myeloid involvement is required to distinguish MLN-TKs from de novo B-lymphoblastic leukemia, T-lymphoblastic leukemia/lymphoma, and histiocytic proliferations harboring identical fusions.
    CONCLUSIONS: Recognition of MLN-TK requires integrating clinical context, morphology, cytogenetics, and molecular pathology. Precise identification of the TK gene and partner, disease phase, and lineage is essential for classification, TKI selection, transplant planning, and measurable residual disease monitoring.
    Keywords:  Myeloid/lymphoid neoplasm; leukemia; mixed phenotype; tyrosine kinase fusion
    DOI:  https://doi.org/10.1093/ajcp/aqag119
  17. Am J Hematol. 2026 Nov 06.
    Use of RBC Parameters to Establish Functional Ferritin Cutoffs for the Potential Diagnosis of Iron Deficiency in Adults and Children.
    Edward C C Wong, Ky Van, Zhen Chen, Caixia Bi, Lance Bare.
      
    DOI:  https://doi.org/10.1002/ajh.70549
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