JAK2V617F 会损害骨髓增殖性肿瘤中的淋巴分化

IF 12.8 1区 医学 Q1 HEMATOLOGY Leukemia Pub Date : 2024-09-07 DOI:10.1038/s41375-024-02388-3
Daniel C. Choi, Nassima Messali, Narasimha Rao Uda, Ghaith Abu-Zeinah, Pouneh Kermani, Maria Mia Yabut, Heidi E. L. Lischer, Franco Castillo Tokumori, Katie Erdos, Thomas Lehmann, Marta Sobas, Tata Nageswara Rao, Joseph M. Scandura
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引用次数: 0

摘要

骨髓增殖性肿瘤(MPNs)源于单个造血干细胞(HSC)获得驱动突变,通常在临床表现前数十年就已发生[1]。最常见的驱动突变是JAK2V617F,它通过对骨髓造血至关重要的受体激活异常的JAK/STAT信号[2]。随着时间的推移,这种 MPN 造血干细胞克隆会取代正常的造血干细胞克隆,导致骨髓细胞过度生成。然而,淋巴细胞减少症也可见于 MPN 患者[3, 4],并导致中性粒细胞与淋巴细胞比值(NLR)升高,而 NLR 可预测疾病相关并发症,包括血栓形成和死亡率[5, 6]。为了评估 JAK2V617F 对 MPN 队列中造血的影响,我们通过荧光激活细胞分选 (FACS) 技术,用液滴数字 PCR 测量了从外周血 (PB) 中分馏出的造血亚群中的 JAK2V617F 突变等位基因频率 (MAF)。造血干细胞和多能祖细胞(造血干细胞/多能祖细胞,CD45dimCD34+CD38-CD45RA-)的MAF在MPN病程的每一年增加1.6%(±0.5%)(图1B)。尽管 JAK2V617F 在造血过程中逐渐占据主导地位,但正如之前所报道的那样,JAK2V617F 在淋巴细胞中基本不存在(图 1C 和补充图 1)[9]。因此,淋巴细胞生成不足可能会导致 JAK2V617F 多发性骨髓瘤中的淋巴细胞减少症。
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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JAK2V617F impairs lymphoid differentiation in myeloproliferative neoplasms
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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