NAM-NAD+-ADO metabolic reprogramming is a key factor for DNMT3A mutation to promote leukemia development through regulating cell cycle and immune microenvironment
Abstract:DNMT3A-R882H mutation is a frequent epigenetic mutation in acute myeloid leukemia (AML)-M4 and M5, participating in the regulation of cell growth and differentiation by blocking the binding of transcription factor complexes to DNA. However, effective approaches that directly target this inactivating mutation for therapy remain lacking. For the first time, we show that the DNMT3A-R882H mutation can switch leukemia cells to undergo nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD+) metabolism and in… Show more
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