Cytogenetic and Molecular Genetic Driven Prediction of Response to First-Treatment and Prognosis in Acute Myeloid Leukemia: A Retrospective Cohort Study

IF 2.8 2区医学 Q2 GENETICS & HEREDITY

Genes, Chromosomes & Cancer Pub Date : 2025-09-22 DOI:10.1002/gcc.70081

Henan Zhang, Xuan Liu, Xiaoning Wang, Qiang Zhang, Beibei Xin, Yiyang Shen, Pengcheng He, Jihong Zhang

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引用次数: 0

Abstract

Background

The first induction therapy is critical in determining subsequent treatment strategies and patient outcomes in acute myeloid leukemia (AML). This study aimed to comprehensively analyze the genetic landscape of AML patients to construct risk prediction models for the first-treatment response.

Methods

A total of 921 adult AML patients (Cohort 1) were included to characterize the genetic landscape and explore the correlations among genetic features in AML. To ensure the generalizability of the risk prediction models, 62 AML patients (Cohort 2) from another center were included in the modeling analysis. Risk prediction models for the first-treatment response were constructed using multivariable logistic regression with bootstrapping validation, and their impact on prognosis was also assessed.

Results

The cohort exhibited cytogenetic abnormalities, with favorable, intermediate, and adverse-risk features for 15.9%, 67.5%, and 16.5%, respectively. The top mutation genes were NPM1, FLT3-ITD, and NRAS. The top single nucleotide polymorphisms (SNPs) sites were GATA2 rs2335052, TP53 rs1042522, and TET2 rs2454206. Risk assessment models showed that for the intensive chemotherapy group, t(16;16) (p13; q22), CEBPA bZIP in-frame, and NPM1 type A were favorable factors, while trisomy 22, TET2, FLT3-ITD, FLT3 p.D835, ASXL1 rs750318549, and TP53 were unfavorable factors. For the non-intensive chemotherapy group, normal karyotypes and all CEBPA mutations were favorable factors. Calibration curves revealed an area under the receiver operating characteristic curve (AUC) of 73.3% for the intensive chemotherapy cohort and 66.1% for the low-intensive chemotherapy cohort. Among non-transplanted patients, significantly longer overall survival (OS) and progression-free survival (PFS) were observed in those predicted to achieve complete remission (CR)/CR with incomplete count recovery (CRi) compared to those predicted to not achieve CR/CRi.

Conclusion

This study first explores the combined role of karyotypes, mutations, and SNPs in AML treatment, offering valuable risk prediction models for guiding strategies.

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细胞遗传学和分子遗传学驱动的急性髓系白血病首次治疗反应和预后预测：一项回顾性队列研究

背景：急性髓性白血病（AML）的首次诱导治疗是决定后续治疗策略和患者预后的关键。本研究旨在全面分析AML患者的遗传格局，构建首次治疗反应的风险预测模型。方法对921例成年AML患者（队列1）进行遗传景观分析，探讨AML遗传特征之间的相关性。为了确保风险预测模型的通用性，来自另一个中心的62例AML患者（队列2）被纳入建模分析。采用多变量logistic回归建立首次治疗反应的风险预测模型，并进行自适应验证，并评估其对预后的影响。结果该队列显示细胞遗传学异常，有利、中等和不良风险特征分别为15.9%、67.5%和16.5%。顶端突变基因为NPM1、FLT3-ITD和NRAS。单核苷酸多态性位点最高的是GATA2 rs2335052、TP53 rs1042522和TET2 rs2454206。风险评估模型显示，在强化化疗组，t(16;16) （p13; q22）、CEBPA bZIP in-frame、NPM1 A型是有利因素，而22三体、TET2、FLT3- itd、FLT3 p.D835、ASXL1 rs750318549、TP53是不利因素。对于非强化化疗组，正常核型和所有CEBPA突变都是有利因素。校准曲线显示，强化化疗组的受试者工作特征曲线（AUC）下面积为73.3%，低强化化疗组为66.1%。在非移植患者中，与未实现完全缓解(CR)/计数恢复不完全（CRi）的患者相比，预测实现完全缓解(CR)/计数恢复不完全（CRi）的患者的总生存期（OS）和无进展生存期（PFS）明显更长。本研究首次探讨了核型、突变和snp在AML治疗中的联合作用，为指导策略提供了有价值的风险预测模型。

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

Genes, Chromosomes & Cancer 医学-遗传学

CiteScore

7.00

自引率

8.10%

发文量

审稿时长

4-8 weeks

期刊介绍： Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.