Smc3Haploinsufficiency and Smc3Deletion Alter Hematopoiesis In Vivo

Recurrent mutations in SMC3, encoding a cohesin subunit, have been identified in acute myeloid leukemia (AML) and other myeloid malignancies by our group and others. SMC3mutations are heterozygous in AML patients. Missense, nonsense, and splice site mutations have been observed across all domains of SMC3. Given the breath of mutations, it is important to determine whether these represent recurrent loss-of-function mechanisms, or if some might have dominant negative effects. To determine the impact of Smc3deletion on hematopoiesis, we studied both Smc3haploinsufficient and Smc3deficient mice as models of loss-of function and dominant negative phenotypes respectively.