Cohesin haploinsufficiency is tolerated in Cbfb::MYH11-driven murine acute myeloid leukemia.

ABSTRACT: Cohesin gene mutations occur in many malignancies, including acute myeloid leukemia (AML). Loss-of-function mutations in the four major cohesin complex genes (RAD21, SMC3, SMC1a, and STAG2) occur across most major genetic subtypes of AML but are notably absent in AML harboring CBFB::MYH11, suggesting that cohesin mutations yield distinct biological outcomes dependent on the genetic AML driver. We hypothesized that CBFB::MYH11-expressing leukemias would be dependent on intact cohesin genes given their near-mutual exclusivity. To investigate this, we combined either germline or inducible heterozygous deletions in cohesin genes Smc3 or Rad21, respectively, with an inducible murine model of Cbfb::MYH11 AML. This approach allowed us to evaluate the effects of cohesin haploinsufficiency on leuke

SUBMITTER: Conneely SE 

PROVIDER: S-EPMC12672056 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature