Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics Pub Date : 2025-09-18 DOI:10.1016/j.cancergen.2025.09.008

Wanfang Yang , Jing Xu , Shuhua Cao , Ning Wang , Zhuanghui Hao , Qing Wang , Yanhong Tan , Xiuhua Chen , Zhifang Xu , Yaofang Zhang , Jianmei Chang , Xiaojuan Wang , Fanggang Ren , Hongwei Wang

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引用次数: 0

Abstract

Mutations in Isocitrate Dehydrogenase-1 (IDH1) and IDH2 lead to abnormal histone hypermethylation and DNA modifications, disrupting cell differentiation, yet the clinical and prognostic significance of these mutations in primary acute myeloid leukemia (AML) remains debated. This study retrospectively analyzed 181 newly diagnosed AML patients, categorizing them into IDH1mut, IDH2mut, and IDHwt groups to compare clinical features, mutational profiles, and outcomes. IDH1 and IDH2 mutations were detected in 7.7 % (14/181) and 11.6 % (21/181) of cases, respectively. Patients with IDH mutations were older, had higher platelet counts, elevated WT1 mRNA expression, and lower white blood cell counts compared to IDHwt patients. Notably, IDH1mut patients showed no significant OS difference (P = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008–3.792, P = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (P = .013 and P = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (P < .05).

These findings suggest that early detection of IDH1/2 mutations and associated clinical features at AML diagnosis could provide a rationale for targeted therapy with IDH inhibitors, potentially improving patient outcomes.

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IDH1/2突变对成人急性髓性白血病患者预后的差异影响

异柠檬酸脱氢酶-1 （IDH1）和IDH2突变导致异常组蛋白超甲基化和DNA修饰，破坏细胞分化，但这些突变在原发性急性髓性白血病（AML）中的临床和预后意义仍存在争议。本研究回顾性分析了181例新诊断的AML患者，将他们分为IDH1mut、IDH2mut和IDHwt组，比较临床特征、突变谱和结局。IDH1和IDH2突变分别占7.7%（14/181）和11.6%（21/181）。与IDHwt患者相比，IDH突变患者年龄较大，血小板计数较高，WT1 mRNA表达升高，白细胞计数较低。值得注意的是，IDH1mut患者的总生存期（OS）无显著差异（P = 0.153），而IDH2mut患者的总生存期（OS）明显短于IDHwt患者（HR = 1.844, 95% CI: 1.008-3.792, P = 0.047）。此外，DNMT3A共突变的IDH1mut患者的DFS和OS也较短（P = 0.013和P = 0.003），而NPM1、ASXL1或SRSF2共突变的IDH2mut患者的无病生存期（DFS）和OS较低（P < 0.05）。这些发现表明，在AML诊断中早期检测IDH1/2突变和相关临床特征可以为IDH抑制剂靶向治疗提供理论依据，可能改善患者的预后。

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 Genetics ONCOLOGY-GENETICS & HEREDITY

CiteScore

3.20

自引率

5.30%

发文量

167

审稿时长

27 days

期刊介绍： The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.