CASE REPORT article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1622820
This article is part of the Research TopicMyelodysplastic Neoplasm and Acute Myeloid Leukemia: Multi-Omics Approaches and Precision MedicineView all 6 articles
Case Report: Myelodysplastic/Myeloproliferative Neoplasm with Concurrent SF3B1, ASXL1, JAK2 and CBL Mutations and <15% Bone Marrow Ringed Sideroblasts
Provisionally accepted
- 1Yanbian University, Yanji, China
- 2Yanbian University Hospital, Yanji, China
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This first-reported case of SF3B1-mutated myelodysplastic/myeloproliferative neoplasm (MDS/MPN-SF3B1-T) with coexisting ASXL1, JAK2 p.R683G, and CBL mutations challenges conventional genomic prognostic paradigms. A 72-year-old woman presented with anemia (Hb 91 g/L), thrombocytosis (502×10⁹/L), and 10% bone marrow ring sideroblasts, fulfilling 2022 WHO diagnostic criteria through molecular precedence of SF3B1 p.K700E (VAF 40.5%) despite subthreshold sideroblasts. Comprehensive genomic profiling revealed a unique quadruple mutation signature: ASXL1 p.G646Wfs*12 (19.8% VAF), JAK2 p.R683G (17.5%), and CBL p.R149Q (16.2%), with preserved karyotype. Functional analyses demonstrated mutation-specific pathobiological crosstalk: 1) SF3B1-mediated mitochondrial iron mislocalization (ALAS2 splicing defects, ABCB7 downregulation) synergized with ASXL1-driven epigenetic repression of erythroid transcription factors (GATA1，KLF1), exacerbating anemia; 2) JAK2 p.R683G's partial kinase activation combined with CBL-dependent RAS/MAPK signaling sustained thrombocytosis through megakaryocytic hyperplasia. Despite harboring high-risk ASXL1 truncation, the patient maintained hematologic stability for six months without therapy, exhibiting declining platelet counts and improving Hb. This apparent genotype-phenotype discordance was attributed to clonal equilibrium (SF3B1 dominance suppressing ASXL1 leukemogenicity) and mutation-specific signaling attenuation (JAK2 R683G's suboptimal kinase activation). The case provides three key advances: 1) validates WHO 2022's molecular-centric classification by resolving <15% sideroblast diagnostic dilemmas, 2) redefines thrombocytosis mechanisms in overlap syndromes through JAK2/CBL comutation dynamics, and 3) advocates geriatric-specific risk stratification incorporating clonal architecture over mutation burden. Our findings necessitate revision of therapeutic algorithms for molecularly complex, treatment-naï ve elderly patients, particularly in resource-limited settings where socioeconomic factors critically influence management strategies.
Keywords: Myelodysplastic/Myeloproliferative Neoplasm (MDS/MPN), SF3B1 mutation, JAK2 mutation, <15% Bone Marrow Ringed Sideroblasts, WHO Classification Criteria
Received: 04 May 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Wang and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shengyu Jin, Yanbian University Hospital, Yanji, China
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