Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features.

ABSTRACT: Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient heterogeneity. We show that subtypes prone to shift from the B-lineage (for example BCR::ABL1, KMT2A-R and DUX4-R B-ALL) are enriched for multipotent progenitors and show this developmental stage exhibits CEBPA activation and retains myeloid potential, providing a mechanistic explanation for this clinical

SUBMITTER: Iacobucci I 

PROVIDER: S-EPMC12377259 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature