Mitochondrial carrier homolog 2 is necessary for AML survival

Dilshad H Khan, Michael Mullokandov, Yan Wu, Veronique Voisin, Marcela Victoria Gronda, Rose Hurren, Xiaoming Wang, Neil MacLean, Danny V Jeyaraju, Yulia Jitkova, G Wei Xu, Rob C Laister, Ayesh Seneviratne, Zachary Blatman, Troy Ketala, Gary D Bader, Sajid A Marhon, Daniel D De Carvalho, Mark D Minden, Atan GrossAaron D Schimmer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)81-92
Number of pages12
JournalBlood
Volume136
Issue number1
Early online date16 Apr 2020
DOIs
StatePublished - 2 Jul 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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