| Literature DB >> 32299104 |
Dilshad H Khan1, Michael Mullokandov2, Yan Wu1, Veronique Voisin3, Marcela Gronda1, Rose Hurren1, Xiaoming Wang1, Neil MacLean1, Danny V Jeyaraju1, Yulia Jitkova1, G Wei Xu1, Rob Laister1, Ayesh Seneviratne1, Zachary M Blatman1, Troy Ketela1, Gary D Bader3,4, Sajid A Marhon1, Daniel D De Carvalho1, Mark D Minden1, Atan Gross2, Aaron D Schimmer1.
Abstract
Through a clustered regularly insterspaced short palindromic repeats (CRISPR) screen to identify mitochondrial genes necessary for the growth of acute myeloid leukemia (AML) cells, we identified the mitochondrial outer membrane protein mitochondrial carrier homolog 2 (MTCH2). In AML, knockdown of MTCH2 decreased growth, reduced engraftment potential of stem cells, and induced differentiation. Inhibiting MTCH2 in AML cells increased nuclear pyruvate and pyruvate dehydrogenase (PDH), which induced histone acetylation and subsequently promoted the differentiation of AML cells. Thus, we have defined a new mechanism by which mitochondria and metabolism regulate AML stem cells and gene expression.Entities:
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Year: 2020 PMID： 32299104 DOI： 10.1182/blood.2019000106
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113