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Transcriptomic effects of nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion on human AML cells

ABSTRACT: Through integration of whole genome CRISPR screening and pan-cancer genetic dependency mapping, we identified nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) as acute myeloid leukemia (AML) dependencies governing NAD+ biosynthesis. While both NAMPT and NMNAT1 were required for AML, we found that the presence of NAD+ precursors bypassed the dependence of AML on NAMPT, but not NMNAT1, pointing to NMNAT1 as a gatekeeper of NAD+ biosynthesis. We provide evidence that reduced nuclear NAD+ upon deletion of NMNAT1 activated p53, which is due to attenuated deacetylation by SIRT6/7 in AML cells. Our findings reveal that NAD+ is a critical metabolic foundation for AML, and NMNAT1 is a novel therapeutic target for this disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171565 | GEO | 2021/07/28

REPOSITORIES: GEO

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The role of nicotinamide phosphoribosyltransferase (Nampt) in hippocampal neural stem/progenitor cells

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Nicotinamide mononucleotide, a key NAD+ precursor, treats the pathophysiology of diet- and age-induced diabetes

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The role of nicotinamide phosphoribosyltransferase (Nampt) in hippocampal neural stem/progenitor cells

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Transcriptomic effects of nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion on human AML cells

Project description:Transcriptomic effects of nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion on human AML cells

| PRJNA720103 | ENA

Epigenetic regulation of NfatC1 transcription and osteoclastogenesis by nicotinamide phosphoribosyl transferase in the pathogenesis of arthritis

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