急性髓系白血病中核磷蛋白（NPM1）的综合基因组分析

A Comprehensive Genomic Analysis of Nucleophosmin (NPM1) in Acute Myeloid Leukemia.

作者信息

Batayneh Osama, Moein Mahmoudreza, Goodman Alexandra, Desai Devashish, Pavlick Dean, Marcus Chelsea, Ho Caleb, Madison Russell, Huang Richard S P, Ross Jeffrey S, Gentile Teresa, Zhou Zheng, Ghimire Krishna Bilas

机构信息

Department of Medicine, Division of Hematology/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.

SUNY Upstate Medical University, Syracuse, NY 13210, USA.

出版信息

Cancers (Basel). 2025 Aug 20;17(16):2710. doi: 10.3390/cancers17162710.

DOI:10.3390/cancers17162710

PMID:40867339

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12384262/

Abstract

This study investigates genomic alterations (GA) between NPM1-mutated (NPM1mut) and wild-type (NPM1wt) acute myeloid leukemia (AML), aiming to better understand the AML genomic profile. NPM1mut AML represents a distinct clinical AML subtype with high relapse rates despite initial responsiveness to chemotherapy. A total of 4206 AML cases from 2019 to 2024 were analyzed using the FoundationOne Heme assay, incorporating comprehensive DNA and RNA sequencing. Patients were stratified into NPM1mut and NPM1wt cohorts, and genomic differences were systematically compared between the two groups. Among 4206 cases, 633 (15.1%) featured GA, with over 99% exhibiting short variant mutations. NPM1mut AML was more common in females (53.4% vs. 41.5%) and associated with a slightly higher median age (62 vs. 60 years). GA was more frequent in NPM1mut AML compared to the NPM1wt and included (39.2% vs. 12.6%; < 0.0001), PTPN11 (18.3% vs. 7.5%; < 0.0001), (54.5% vs. 14.7%; < 0.0001), (16.1% vs. 5.6%; < 0.0001), (19.0% vs. 9.0%; < 0.0001), TET2 (23.4% vs. 13.5%; < 0.0001), and (12.5% vs. 9.4%; = 0.02). GA was more frequent in NPM1wt AML and included (17.1% vs. 3.6%; 0.0001), (7.5% vs. 1.6%; < 0.0001), (14.7% vs. 0.2%; < 0.0001), (22.5% vs. 1.9%; 0.0001), (6.9% vs. 1.6%; < 0.0001) and (19.1% vs. 4.1%; < 0.0001). Mutations linked to therapy targets in AML, such as ( and ), , and (both associated with inferior outcomes), are more commonly observed in NPM1mut AML, whereas , , and myelodysplastic-related mutations are more commonly observed in NPM1wt AML.

摘要

本研究调查了NPM1突变型（NPM1mut）与野生型（NPM1wt）急性髓系白血病（AML）之间的基因组改变（GA），旨在更好地了解AML的基因组图谱。NPM1mut AML代表一种独特的临床AML亚型，尽管初始对化疗有反应，但复发率很高。使用FoundationOne Heme检测法对2019年至2024年的4206例AML病例进行了分析，该检测法纳入了全面的DNA和RNA测序。患者被分为NPM1mut和NPM1wt队列，并系统地比较了两组之间的基因组差异。在4206例病例中，633例（15.1%）存在GA，超过99%表现为短变异突变。NPM1mut AML在女性中更常见（53.4%对41.5%），且与略高的中位年龄相关（62岁对60岁）。与NPM1wt相比，GA在NPM1mut AML中更频繁，包括（39.2%对12.6%；<0.0001）、PTPN11（18.3%对7.5%；<0.0001）（54.5%对14.7%；<0.0001）、（16.1%对5.6%；<0.0001）、（19.0%对9.0%；<0.0001）、TET2（23.4%对13.5%；<0.0001）以及（12.5%对9.4%；=0.02）。GA在NPM1wt AML中更频繁，包括（17.1%对3.6%；0.0001）、（7.5%对1.6%；<0.0001）、（14.7%对0.2%；<0.0001）、（22.5%对1.9%；0.0001）、（6.9%对1.6%；<0.0001）以及（19.1%对4.1%；<0.0001）。与AML治疗靶点相关的突变，如（和）、、以及（均与较差的预后相关），在NPM1mut AML中更常见，而、以及与骨髓增生异常相关的突变在NPM1wt AML中更常见。