真性红细胞增多症的突变景观：表型、基因型和预后相关因素。

IF 10.1 1区医学 Q1 HEMATOLOGY

American Journal of Hematology Pub Date : 2025-05-15 DOI:10.1002/ajh.27717

Masooma S Rana,Moazah Iftikhar,Yamna Jadoon,Maymona Abdelmagid,David S Viswanatha,Rong He,Kaaren K Reichard,Animesh D Pardanani,Naseema Gangat,Ayalew Tefferi

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引用次数: 0

摘要

真性红细胞增多症（PV）总是与JAK2突变相关，超过50%的患者携带额外的非JAK2突变。在目前的研究中，319例PV患者在诊断时或在PV慢性期（A组：N = 270, 85%）或在纤维化时(B组；N = 37, 12%)或白血病(C组；N = 12, 4%)转化。TP53/SRSF2/IDH1/U2AF1的突变频率在互斥的A组（2%/4%/2%/0.4%）、B组（8%/0%/0%/5%）和C组（50%/25%/17%/8%）患者之间差异有统计学意义（p < 0.05）。表型/基因型相关性分析以及对总体（OS）、无白血病（LFS）和无骨髓纤维化（MFFS）生存的预后影响仅限于A组患者。ASXL1MUT与低龄相关（p < 0.01）， SRSF2MUT与高龄和白细胞增多相关（p < 0.01）， TP53MUT与白细胞增多相关（p < 0.01）。ASXL1与IDH2 （p < 0.01）、SRSF2 （p < 0.01）、SRSF2与IDH2 （p < 0.01）、TP53与NRAS （p = 0.01）突变共分离明显。多变量分析鉴定SRSF2MUT (p < 0.01；HR, 4.2, 1.9-9.5), IDH2MUT (p = 0.01；HR, 5.3, 1.8-15.3), ASXL1MUT (p = 0.04；人力资源,2.0,1.1 - -3.7),白细胞数≥15×109 / L (p < 0.01;HR 2.0, 1.3-3.1)和高龄（p < 0.01）为OS的危险因素。存在时的中位OS (N = 235；87%)或缺席(N = 35；任何不良突变（即SRSF2MUT， ASXL1MUT或IDH2MUT）的发生率分别为8.8年和17.8年(p = 0.01；Hr 1.8, 1.1-2.9)。此外，ASXL1MUT (p = 0.02；HR, 1.6-24.9), SRSF2MUT (p = 0.06；HR, 11.9, 1.1-126.2)和高龄（p = 0.04）与较差的LFS相关，SRSF2MUT (p < 0.01；HR, 24.0, 5.5 ~ 103.8)，核型异常(p < 0.01；HR 3.8, 1.6-8.9)， MFFS较差。在单变量分析中，非jak2突变的数量在预测预后方面具有重要意义，而在多变量分析中则没有。当前研究的观察结果强调了PV中非jak2突变的预后意义，以及将其纳入未来预后模型的前景。

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The Mutational Landscape in Polycythemia Vera: Phenotype, Genotype, and Prognostic Correlates.

Polycythemia vera (PV) is invariably associated with a JAK2 mutation, with over 50% of patients harboring additional non-JAK2 mutations. In the current study, 319 patients with PV underwent NGS at diagnosis or in chronic phase PV (Group A: N = 270, 85%) or at the time of fibrotic (Group B; N = 37, 12%) or leukemic (Group C; N = 12, 4%) transformation. Mutational frequencies involving TP53/SRSF2/IDH1/U2AF1 were significantly (p < 0.05) different between patients in the mutually exclusive Groups A (2%/4%/2%/0.4%), B (8%/0%/0%/5%), and C (50%/25%/17%/8%). Analyses on phenotype/genotype associations and prognostic impact on overall (OS), leukemia-free (LFS), and myelofibrosis-free (MFFS) survival were limited to Group A patients. ASXL1MUT was associated with younger age (p < 0.01), SRSF2MUT with older age and leukocytosis (p < 0.01), and TP53MUT with leukocytosis (p < 0.01). Mutation co-segregation was apparent between ASXL1 and IDH2 (p < 0.01) or SRSF2 (p < 0.01), SRSF2 and IDH2 (p < 0.01), and TP53 and NRAS (p = 0.01). Multivariable analysis identified SRSF2MUT (p < 0.01; HR, 4.2, 1.9-9.5), IDH2MUT (p = 0.01; HR, 5.3, 1.8-15.3), ASXL1MUT (p = 0.04; HR, 2.0, 1.1-3.7), leukocyte count ≥ 15 × 109/L (p < 0.01; HR 2.0, 1.3-3.1), and advanced age (p < 0.01) as risk factors for OS. Median OS in the presence (N = 235; 87%) or absence (N = 35; 13%) of any adverse mutation (i.e., SRSF2MUT, ASXL1MUT, or IDH2MUT) was 8.8 versus 17.8 years (p = 0.01; HR 1.8, 1.1-2.9). In addition, ASXL1MUT (p = 0.02; HR, 1.6-24.9), SRSF2MUT (p = 0.06; HR, 11.9, 1.1-126.2), and advanced age (p = 0.04) were associated with inferior LFS, and SRSF2MUT (p < 0.01; HR, 24.0, 5.5-103.8) and abnormal karyotype (p < 0.01; HR 3.8, 1.6-8.9) with inferior MFFS. The number of non-JAK2 mutations was significant in predicting outcome in univariate but not multivariable analysis. The observations from the current study highlight the prognostic significance of non-JAK2 mutations in PV and the prospect of their inclusion in future prognostic models.

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来源期刊

American Journal of Hematology 医学-血液学

CiteScore

15.70

自引率

3.90%

发文量

363

审稿时长

3-6 weeks

期刊介绍： The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.