- Mitochondrial carrier homolog 2 is necessary for AML survival.
Mitochondrial carrier homolog 2 is necessary for AML survival.
Blood (2020-04-17)
Dilshad H Khan, Michael Mullokandov, Yan Wu, Veronique Voisin, Marcela Gronda, Rose Hurren, Xiaoming Wang, Neil MacLean, Danny V Jeyaraju, Yulia Jitkova, G Wei Xu, Rob Laister, Ayesh Seneviratne, Zachary M Blatman, Troy Ketela, Gary D Bader, Sajid A Marhon, Daniel D De Carvalho, Mark D Minden, Atan Gross, Aaron D Schimmer
PMID32299104
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.
MATERIALS