Together, these studies identified DNMT3A as an early leukemia-initiating gene and, more broadly, established CHIP as an asymptomatic potential precursor of myeloid diseases, analogous to monoclonal gammopathy of undetermined significance as a potential precursor of multiple myeloma and monoclonal B cell lymphocytosis as a potential precursor of CLL. Here, DNMT3A is linked to leukemia.