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.