Mitochondrial carrier homolog 2 is necessary for AML survival-Reference-Cited by-同舟云学术

Mitochondrial carrier homolog 2 is necessary for AML survival

Published:2020-07-02 Issue:1 Volume:136 Page:81-92
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Khan Dilshad H.¹,Mullokandov Michael²,Wu Yan¹^ORCID,Voisin Veronique³,Gronda Marcela¹,Hurren Rose¹,Wang Xiaoming¹,MacLean Neil¹,Jeyaraju Danny V.¹,Jitkova Yulia¹,Xu G. Wei¹,Laister Rob¹,Seneviratne Ayesh¹,Blatman Zachary M.¹,Ketela Troy¹,Bader Gary D.³⁴,Marhon Sajid A.¹^ORCID,De Carvalho Daniel D.¹^ORCID,Minden Mark D.¹,Gross Atan²,Schimmer Aaron D.¹

Affiliation:

1. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;

2. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel;

3. The Donnelly Centre, University of Toronto, Toronto, ON, Canada; and

4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/136/1/81/1747596/bloodbld2019000106.pdf

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