Non- MPL-W515K/L mutations in myeloproliferative neoplasms: insights from two case reports and a review of the literature.

IF 2.1 4区医学 Q2 HEMATOLOGY

Expert Review of Hematology Pub Date : 2025-06-27 DOI:10.1080/17474086.2025.2527345

Ane Sofie Tønne Nesse, Hilde Kollsete Gjelberg, Miriam Sandnes, Rakel Brendsdal Forthun, Håkon Reikvam

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引用次数: 0

Abstract

Background: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) result from clonal proliferation of hematopoietic stem cells, and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Key driver mutations in the JAK2, CALR, and MPL genes are important for diagnosis and differentiation of triple-negative cases. The MPL gene, particularly exon 10, harbors mutation hotspots influencing pathogenesis and prognosis.

Research designand methods: Thisstudy presents two cases of atypical MPLmutations in MPN-patients and investigates the prevalence ofnon-canonical MPLmutationsin the literature.

Results: Wereport two MPN cases with non-canonical MPLmutations (S204P and W515R) detected by next-generation sequencing.We also conducted a systematic review of the PubMed database,identifying 68 cases of non-W515L/K MPLmutations. A total of 86 mutations were identified, comprised of 32unique non-canonical mutations. W515R/S/A were the most frequent(31%), followed by V501A/M (15%) and S505N/C (13%). 59% of patientshad ET, 24% PMF and 13% post-ET/PV MF. Most mutations (71%) occurredin exon 10. 26% harbored concurrent JAK2,CALR andMPLmutations.

Conclusions: Ourfindings highlight the importance of non-canonical mutations indiagnosis of MPN to prevent misclassification and improve patientmanagement. Understanding these mutations could lead to more tailoredtreatments and better outcomes in MPN patients.

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骨髓增殖性肿瘤中的非MPL-W515K/L突变：来自两个病例报告和文献综述的见解

背景：费城染色体阴性骨髓增生性肿瘤（mpn）是由造血干细胞克隆性增殖引起的，包括真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）。JAK2、CALR和MPL基因的关键驱动突变对三阴性病例的诊断和分化很重要。MPL基因，特别是外显子10，蕴藏着影响发病和预后的突变热点。研究设计和方法：本研究报告了两例mpn患者的非典型mpl突变，并调查了文献中非典型mpl突变的流行情况。结果：新一代测序检测到2例非典型mpl突变（S204P和W515R）的MPN病例。我们还对PubMed数据库进行了系统回顾，确定了68例非w515l /K MPLmutations。共鉴定出86个突变，包括32个独特的非典型突变。W515R/S/A最常见（31%），其次是V501A/M（15%）和S505N/C（13%）。59%的患者有ET， 24%的患者有PMF， 13%的患者有ET/PV后MF。大多数突变（71%）发生在外显子10。26%的人同时携带JAK2、CALR和mplt突变。结论：我们的研究结果强调了非典型突变诊断MPN对于防止误诊和改善患者管理的重要性。了解这些突变可以为MPN患者带来更有针对性的治疗和更好的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.