在接受VEN-AZA治疗的新诊断急性髓系白血病患者中，SRSF2基因突变的预后较差。

Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia.

作者信息

Berton Guillaume, Sedaki Bochra, Collomb Erwann, Benachour Sami, Loschi Michael, Mohty Bilal, Saillard Colombe, Hicheri Yosr, Rouzaud Camille, Maisano Valerio, Villetard Ferdinand, Corda Evelyne D 'Incan, Charbonnier Aude, Rey Jerome, Hospital Marie-Anne, Ittel Antoine, Abbou Norman, Fanciullino Raphaelle, Dadone-Montaudié Bérengère, Vey Norbert, Venton Geoffroy, Cluzeau Thomas, Alary Anne-Sophie, Garciaz Sylvain

机构信息

Department of Hematology, Institut Paoli-Calmettes, Marseille, France.

Department of Hematology, University Hospital Centre L'Archet, Nice, France.

出版信息

Leuk Res. 2024 Jun;141:107500. doi: 10.1016/j.leukres.2024.107500. Epub 2024 Apr 15.

DOI:10.1016/j.leukres.2024.107500

PMID:38636413

Abstract

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.

摘要

剪接体基因（SRSF2、SF3B1、U2AF1、ZRSR2）突变与接受强化化疗的急性髓系白血病患者较差的预后相关。然而，它们在接受强度较低治疗方案的患者中的预后影响尚不清楚。本研究旨在评估剪接体突变对接受维奈克拉和阿扎胞苷治疗的新诊断急性髓系白血病患者的影响。分析纳入了在3家不同医院接受治疗的117例患者。34例患者至少在一个剪接体基因中存在突变（剪接体突变队列）。K/NRAS突变在剪接体突变队列中更为常见（47%对19%，p=0.0022）。剪接体突变队列和剪接体野生型队列之间的缓解率没有差异。中位随访15个月时，剪接体突变与较低的18个月无白血病生存率相关（p=0.0045）。单独分析剪接体突变时，我们发现SRSF2突变与较差的预后相关（总生存期和无白血病生存率的p值分别为0.034和0.037）。在我们的多变量分析中，这种负面的预后影响仍然存在。我们认为这一发现值得进一步开展旨在克服这种负面影响的研究。