In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy.

ABSTRACT: Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes. Here, we integrate multi-recombinase tools for reversible, sequential mutagenesis from premalignancy to leukemia. We demonstrate that inducible Flt3 mutations differentially cooperate with Dnmt3a, Idh2, and Npm1 mutant alleles, and that changing the order of mutations influences cellular and

SUBMITTER: Bowman RL 

PROVIDER: S-EPMC11561369 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature