剪接因子3b亚基1在骨髓增生异常综合征、急性髓系白血病和慢性淋巴细胞白血病中的突变模式及预后意义：一项对1691例病例的回顾性研究

Splicing factor 3b subunit 1 mutation patterns and prognostic implications in myelodysplastic syndromes, acute myeloid leukemia, and chronic lymphocytic leukemia: A retrospective study of 1691 cases.

作者信息

Qiao Chun, Xia Yi, Guo Zhen, Zhu Liying, Wu Yujie, Qiu Hairong, Wang Yan, Zhu Huayuan, Qian Sixuan, Hong Ming, Zhu Yu, Shen Wenyi, Gong Yuemin, Jin Hui, Fan Lei, Li Jianyong, Yang Yong, He Guangsheng, Miao Yi, Jin Huimin

机构信息

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

出版信息

Cancer. 2025 Aug 1;131(15):e70017. doi: 10.1002/cncr.70017.

DOI:10.1002/cncr.70017

PMID:40693823

Abstract

BACKGROUND

Splicing factor 3b subunit 1 (SF3B1) mutations have been implicated in hematologic malignancies, but the clinical significance of distinct SF3B1 mutation variants remain unclear.

METHODS

The objective of this study was to evaluate clinicopathologic features, mutational profiles, and outcomes of 1691 patients with hematologic malignancies, including myelodysplastic syndromes (MDS; n = 402), acute myeloid leukemia (AML; n = 758), and chronic lymphocytic leukemia (CLL; n = 531).

RESULTS

The frequency of SF3B1-mutated (SF3B1) MDS, AML, and CLL was 70 of 402 patients (17.4%), 23 of 758 patients (3.0%), and 45 of 531 patients (8.5%), respectively. p.K700E was the most prevalent SF3B1 variant and was identified in 43 of 70 of patients with MDS (61.4%), in seven of 23 patients with AML (30.4%), and in 19 of 45 patients with CLL (42.2%). In MDS and AML, TET2 was the most frequent co-mutated gene in patients with SF3B1 disease (20 of 70 patients with MDS [28.6%]; 11 of 23 patients with AML [47.8%]). For patients with SF3B1 CLL, the most common co-mutated genes were ATM (11 of 45; 24.4%) and TP53 (11 of 45; 24.4%). Kaplan-Meier analysis indicated that the SF3B1 p.K700E variant was significantly associated with improved overall survival (OS) and progression-free survival (PFS) in patients who had MDS (p < .001 and p = .016, respectively) but with worse OS and PFS in those who had AML (p = .006 and p = .006, respectively) compared with those who had wild-type SF3B1. In patients who had CLL, p.I704F was associated with reduced OS (p < .001) and p.K700E was associated with a shorter time-to-first treatment (p = .028) compared with those who had wild-type SF3B1. Multivariable analysis identified p.K700E as an independent protective factor for OS in patients with MDS (p = .048) but as an independent risk factor for both OS and PFS in patients with AML (p = .036 and p = .035, respectively) and for the time to first treatment in patients with CLL (p = .033).

CONCLUSIONS

Specific SF3B1 variants should be incorporated into prognostic stratification for hematologic malignancies.

摘要

背景

剪接因子3b亚基1（SF3B1）突变与血液系统恶性肿瘤有关，但不同SF3B1突变变体的临床意义仍不清楚。

方法

本研究的目的是评估1691例血液系统恶性肿瘤患者的临床病理特征、突变谱和预后，这些患者包括骨髓增生异常综合征（MDS；n = 402）、急性髓系白血病（AML；n = 758）和慢性淋巴细胞白血病（CLL；n = 531）。

结果

SF3B1突变（SF3B1）的MDS、AML和CLL患者的频率分别为402例中的70例（17.4%）、758例中的23例（3.0%）和531例中的45例（8.5%）。p.K700E是最常见的SF3B1变体，在70例MDS患者中的43例（61.4%）、23例AML患者中的7例（30.4%）和45例CLL患者中的19例（42.2%）中被鉴定出来。在MDS和AML中，TET2是SF3B1疾病患者中最常见的共突变基因（70例MDS患者中的20例[28.6%]；23例AML患者中的11例[47.8%]）。对于SF3B1 CLL患者，最常见的共突变基因是ATM（45例中的11例；24.4%）和TP53（45例中的11例；24.4%）。Kaplan-Meier分析表明，SF3B1 p.K700E变体与MDS患者的总生存期（OS）改善和无进展生存期（PFS）显著相关（分别为p <.001和p =.016），但与野生型SF3B1的AML患者相比，OS和PFS较差（分别为p =.006和p =.006）。在CLL患者中，与野生型SF3B1相比，p.I704F与OS降低相关（p <.001），p.K700E与首次治疗时间缩短相关（p =.028）。多变量分析确定p.K700E是MDS患者OS的独立保护因素（p =.048），但在AML患者中是OS和PFS的独立危险因素（分别为p =.036和p =.035），在CLL患者中是首次治疗时间的独立危险因素（p =.033）。