Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia.

ABSTRACT: Whole chromosome losses resulting in near-haploid karyotypes are found in a rare subgroup of treatment-refractory acute lymphoblastic leukemia. To systematically dissect the unique physiology and uncover susceptibilities that can be exploited in near-haploid leukemia, we leveraged single-cell RNA-Seq and computational inference of cell cycle stages to pinpoint key differences between near-haploid and diploid leukemia cells. Combining cell cycle stage-specific differential expression with gene essentiality scores from a genome-wide CRISPR-Cas9-mediated knockout screen, we identified the homologous recombination pathway component RAD51B as an essential gene in near-haploid leukemia. DNA damage analyses revealed significantly increased sensitivity of RAD51-mediated repair to RAD51B loss in th

SUBMITTER: Liu-Lupo Y 

PROVIDER: S-EPMC10247733 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature