Smyd3 KO CML mice RNA seq

The development of BCR-ABL tyrosine kinase inhibitors (TKIs) has revolutionized disease management of chronic myeloid leukemia (CML). However, the persistence of leukemia stem cells (LSCs) remains a big barrier to cure. There is an urgent need to identify the regulators uniquely driving LSCs. In this study, we validated the critical role of SET and MYND domain containing 3 (SMYD3) in the maintenance of LSCs in CML. SMYD3 was overexpressed in CML LSCs and enhanced the survival and self-renewal properties of human primary CML CD34+ cells. Loss of Smyd3 greatly blocked leukemogenesis and impaired the self-renewal and disease reconstitution abilities of LSCs in CML mice without affecting normal hematopoiesis. SMYD3 regulated LSCs in a methyltransferase activity-dependent manner.