The two most commonly affected genes in CH, DNMT3A and TET2 exhibit some of the lowest rates of AML progression while the less frequently mutated but still prevalent TP53 and U2AF1 demonstrate a much higher risk of malignant transformation and are associated with poorer AML prognosis.1,13-15 Certain mutations within genes also confer varying risks of progression, such as the DNMT3A R882H mutation—the most prevalent CH mutation overall—which is underrepresented in CH versus AML and myelodysplastic syndrome (MDS), indicating a potential for increased progression risk.16 The gene discussed is DNMT3A; the disease is acute myeloid leukemia.