Monosomy 7/del(7q) cause sensitivity to inhibitors of nicotinamide phosphoribosyltransferase in acute myeloid leukemia.

ABSTRACT:

Abstract

Monosomy 7 and del(7q) (-7/-7q) are frequent chromosomal abnormalities detected in up to 10% of patients with acute myeloid leukemia (AML). Despite unfavorable treatment outcomes, no approved targeted therapies exist for patients with -7/-7q. Therefore, we aimed to identify novel vulnerabilities. Through an analysis of data from ex vivo drug screens of 114 primary AML samples, we discovered that -7/-7q AML cells are highly sensitive to the inhibition of nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is the rate-limiting enzyme in the nicotinamide adenine dinucleotide salvage pathway. Mechanistically, the NAMPT gene is located at 7q22.3, and deletion of 1 copy due to -7/-7q results in NAMPT haploinsufficiency, leading to reduced expression and a therapeutically targe

SUBMITTER: Eldfors S 

PROVIDER: S-EPMC10987804 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature