小柯机器人

美国科罗拉多大学丹佛分校Craig T. Jordan、Courtney L. Jones等研究人员合作发现，烟酰胺代谢介导复发急性髓样白血病干细胞的维奈克拉耐药。2020年8月20日，《细胞—干细胞》在线发表了这一成果。

Title: Nicotinamide Metabolism Mediates Resistance to Venetoclax in Relapsed Acute Myeloid Leukemia Stem Cells

Author: Courtney L. Jones, Brett M. Stevens, Daniel A. Pollyea, Rachel Culp-Hill, Julie A. Reisz, Travis Nemkov, Sarah Gehrke, Fabia Gamboni, Anna Krug, Amanda Winters, Shanshan Pei, Annika Gustafson, Haobin Ye, Anagha Inguva, Maria Amaya, Mohammad Minhajuddin, Diana Abbott, Michael W. Becker, James DeGregori, Clayton A. Smith, Angelo D’Alessandro, Craig T. Jordan

Issue&Volume: 2020-08-20

Abstract: We previously demonstrated that leukemia stem cells (LSCs) in de novo acute myeloid leukemia (AML) patients are selectively reliant on amino acid metabolismand that treatment with the combination of venetoclax and azacitidine (ven/aza) inhibitsamino acid metabolism, leading to cell death. In contrast, ven/aza fails to eradicateLSCs in relapsed/refractory (R/R) patients, suggesting altered metabolic properties.Detailed metabolomic analysis revealed elevated nicotinamide metabolism in relapsedLSCs, which activates both amino acid metabolism and fatty acid oxidation to driveOXPHOS, thereby providing a means for LSCs to circumvent the cytotoxic effects ofven/aza therapy. Genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase(NAMPT), the rate-limiting enzyme in nicotinamide metabolism, demonstrated selectiveeradication of R/R LSCs while sparing normal hematopoietic stem/progenitor cells.Altogether, these findings demonstrate that elevated nicotinamide metabolism is boththe mechanistic basis for ven/aza resistance and a metabolic vulnerability of R/RLSCs.

DOI: 10.1016/j.stem.2020.07.021

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30359-3

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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