Because two recent IACS-010759 phase I trials reported unexpected side effects that would preclude use of IACS-010759 to treat CH, at least at the doses used in these trials30, we tested metformin, a safe, well-tolerated and commonly used complex I inhibitor, which also targets further genes/pathways identified as Dnmt3a-R882H-specific vulnerabilities in our screen, including mTOR31, STAT532, TGF-β133, GLS34 and Cyclin D complex34. Here, DNMT3A is linked to cyclic hematopoiesis.