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

IF 5.1 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2025-07-22 DOI:10.1002/cncr.70017

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

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引用次数: 0

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^MUT) 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^MUT 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^MUT disease (20 of 70 patients with MDS [28.6%]; 11 of 23 patients with AML [47.8%]). For patients with SF3B1^MUT 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.

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

剪接因子3b亚基1 （SF3B1）突变与血液系统恶性肿瘤有关，但SF3B1突变变体的临床意义尚不清楚。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、突变特征和预后，包括骨髓增生异常综合征(MDS；n = 402)，急性髓性白血病(AML；n = 758)和慢性淋巴细胞白血病(CLL；n = 531)。结果sf3b1突变（SF3B1MUT） MDS、AML和CLL的发生率分别为402例中70例（17.4%）、758例中23例（3.0%）和531例中45例（8.5%）。p.K700E是最常见的SF3B1MUT变异，在70例MDS患者中有43例（61.4%），在23例AML患者中有7例（30.4%），在45例CLL患者中有19例（42.2%）。在MDS和AML患者中，TET2是SF3B1MUT疾病患者中最常见的共突变基因(70例MDS患者中有20例[28.6%]；23例AML患者中有11例（47.8%）。对于SF3B1MUT CLL患者，最常见的共突变基因是ATM (11 / 45；24.4%)和TP53 (11 / 45；24.4%)。Kaplan-Meier分析显示，SF3B1 p.K700E变异与MDS患者总生存期（OS）和无进展生存期（PFS）的改善显著相关(p <；.001和p = .016)，但AML患者的OS和PFS较野生型SF3B1患者差（p = .006和p = .006）。在CLL患者中，p.I704F与OS降低相关(p <；与野生型SF3B1患者相比，p.K700E与较短的首次治疗时间相关（p = 0.028）。多变量分析发现，p.K700E是MDS患者OS的独立保护因素（p = 0.048），但也是AML患者OS和PFS的独立危险因素（p = 0.036和p = 0.035），也是CLL患者首次治疗时间的独立危险因素（p = 0.033）。结论SF3B1特异性变异应纳入血液系统恶性肿瘤的预后分层。

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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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research