CARM1 Is Essential for Myeloid Leukemogenesis but Dispensable for Normal Hematopoiesis

Summary Chromatin-modifying enzymes, and specifically the protein arginine methyltransferases(PRMTs), have emerged as important targets in cancer. Here, we investigated the role of CARM1in normal and malignant hematopoiesis. Using conditional knockout mice, we show that loss of CARM1has little effect on normal hematopoiesis. Strikingly, knockout of Carm1abrogates both the initiation and maintenance of acute myeloid leukemia (AML) driven by oncogenic transcription factors. We show that CARM1knockdown impairs cell-cycle progression, promotes myeloid differentiation, and ultimately induces apoptosis. Finally, we utilize a selective, small-molecule inhibitor of CARM1to validate the efficacy of CARM1inhibition in leukemia cells in vitro and in vivo . Collectively, this work suggests that targeting CARM1may be an effective therapeutic strategy for AML.