接受 VEN-AZA 治疗的新诊断急性髓性白血病患者 SRSF2 基因突变预后不佳

IF 2.1 4区 医学 Q3 HEMATOLOGY Leukemia research Pub Date : 2024-04-15 DOI:10.1016/j.leukres.2024.107500
Guillaume Berton , Bochra Sedaki , Erwann Collomb , Sami Benachour , Michael Loschi , Bilal Mohty , Colombe Saillard , Yosr Hicheri , Camille Rouzaud , Valerio Maisano , Ferdinand Villetard , Evelyne D.'Incan Corda , Aude Charbonnier , Jerome Rey , Marie-Anne Hospital , Antoine Ittel , Norman Abbou , Raphaelle Fanciullino , Bérengère Dadone-Montaudié , Norbert Vey , Sylvain Garciaz
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引用次数: 0

摘要

剪接体基因(SRSF2、SF3B1、U2AF1、ZRSR2)的突变与急性髓性白血病强化化疗患者的不良预后有关。然而,这些基因对接受低强度方案治疗的患者的预后影响却不甚了解。本研究旨在评估Spliceosome突变对接受Venetoclax和阿扎胞苷治疗的新诊断急性髓细胞白血病患者的影响。在3家不同医院接受治疗的117名患者被纳入分析范围。34例患者至少有一个剪接体基因发生突变(剪接体突变队列)。K/NRAS突变在剪接突变队列中更为常见(47% vs 19%,P=0.0022)。剪接突变队列和剪接重组队列的应答率没有差异。中位随访时间为15个月,剪接突变与较低的18个月LFS相关(p=0.0045)。在单独分析剪接突变时,我们发现 SRSF2 突变与较差的预后相关(OS 和 LFS 分别为 p=0.034 和 p=0.037)。在我们的多变量分析中,这种负面预后影响依然存在。我们认为这一发现值得进一步研究,以克服这一负面影响。
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Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia

Mutations in spliceosome genes (SRSF2, SF3B1, U2AF1, ZRSR2) correlate with inferior outcomes in patients treated with intensive chemotherapy for Acute Myeloid Leukemia. However, their prognostic impact in patients treated with less intensive protocols is not well known. This study aimed to evaluate the impact of Spliceosome mutations in patients treated with Venetoclax and Azacitidine for newly diagnosed AML. 117 patients treated in 3 different hospitals were included in the analysis. 34 harbored a mutation in at least one of the spliceosome genes (splice-mut cohort). K/NRAS mutations were more frequent in the splice-mut cohort (47% vs 19%, p=0.0022). Response rates did not differ between splice-mut and splice-wt cohorts. With a median follow-up of 15 months, splice mutations were associated with a lower 18-month LFS (p=0.0045). When analyzing splice mutations separately, we found SRSF2 mutations to be associated with poorer outcomes (p=0.034 and p=0.037 for OS and LFS respectively). This negative prognostic impact remained true in our multivariate analysis. We believe this finding should warrant further studies aimed at overcoming this negative impact.

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来源期刊
Leukemia research
Leukemia research 医学-血液学
CiteScore
4.00
自引率
3.70%
发文量
259
审稿时长
1 months
期刊介绍: Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.
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