GMP-like and MLP-like Subpopulations of Hematopoietic Stem and Progenitor Cells Harboring Mutated <i>EZH2</i> and <i>TP53</i> at Diagnosis Promote Acute Myeloid Leukemia Relapse: Data of Combined Molecular, Functional, and Genomic Single-Stem-Cell Analyses.

ABSTRACT: Acute myeloid leukemia (AML) is associated with unfavorable patient outcomes primarily related to disease relapse. Since specific types of leukemic hematopoietic stem and progenitor cells (HSPCs) are suggested to contribute to AML propagation, this study aimed to identify and explore relapse-initiating HSPC subpopulations present at diagnosis, using single-cell analysis (SCA). We developed unique high-resolution techniques capable of tracking single-HSPC-derived subclones during AML evolution. Each subclone was evaluated for chemo-resistance, in vivo leukemogenic potential, mutational profile, and the cell of origin. In BM samples of 15 AML patients, GMP-like and MLP-like HSPC subpopulations were identified as prevalent at relapse, exhibiting chemo-resistance to commonly used chemotherapy

SUBMITTER: Shahar Gabay T 

PROVIDER: S-EPMC12072498 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature