Although patients with DNMT3A mutations show hepatosplenomegaly and lymphadenopathy due to extramedullary chronic myelomonocytic leukemia (CMML) (13) compared with patients with WT DNMT3A; the signaling pathways that induce such profound hematopoietic dysregulation are poorly understood. The gene discussed is DNMT3A; the disease is chronic myelomonocytic leukemia.