A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.

ABSTRACT: Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases. We identified a bone marrow progenitor (BMP)-like leukemia subpopulation associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL and revealed that NOTCH1 mutations additively drive

SUBMITTER: Xu J 

PROVIDER: S-EPMC11779640 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature