...- Documented pathogenic mutation in cohesin complex including a mutation in STAG2, SMC1A, RAD21, PDS5B, or SMC3 gene from a CLIA-approved test (local testing allowed; will be centrally confirmed)....

Tet2/Stag2 andTet2-mutant clones and the associated hematologic phenotypes were serially transplantable and allowed for genotype-specific in vivo drug testing of the PARP1 inhibitor talazoparib...Forty recipient mice transplanted with Tet2 or Tet2/Stag2 mutant bone marrow cells were stratified into treatment groups with talazoparib or vehicle...To further extend these findings in primary human cells, we developed serially transplantable PDX models of cohesin-mutant AML and performed in vivo drug testing with talazoparib. We noted increased survival of cohesin-mutant PDX models treated with talazoparib as compared to vehicle.