| Literature DB >> 30930145 |
Ayesh K Seneviratne1, Mingjing Xu2, Juan J Aristizabal Henao3, Val A Fajardo4, Zhenyue Hao2, Veronique Voisin5, G Wei Xu2, Rose Hurren2, S Kim2, Neil MacLean2, Xiaoming Wang2, Marcela Gronda2, Danny Jeyaraju2, Yulia Jitkova2, Troy Ketela2, Michael Mullokandov6, David Sharon2, Geethu Thomas2, Raphaël Chouinard-Watkins7, James R Hawley8, Caitlin Schafer9, Helen Loo Yau8, Zaza Khuchua10, Ahmed Aman11, Rima Al-Awar11, Atan Gross6, Steven M Claypool12, Richard P Bazinet7, Mathieu Lupien8, Steven Chan8, Daniel D De Carvalho8, Mark D Minden8, Gary D Bader5, Ken D Stark3, Paul LeBlanc4, Aaron D Schimmer13.
Abstract
Tafazzin (TAZ) is a mitochondrial transacylase that remodels the mitochondrial cardiolipin into its mature form. Through a CRISPR screen, we identified TAZ as necessary for the growth and viability of acute myeloid leukemia (AML) cells. Genetic inhibition of TAZ reduced stemness and increased differentiation of AML cells both in vitro and in vivo. In contrast, knockdown of TAZ did not impair normal hematopoiesis under basal conditions. Mechanistically, inhibition of TAZ decreased levels of cardiolipin but also altered global levels of intracellular phospholipids, including phosphatidylserine, which controlled AML stemness and differentiation by modulating toll-like receptor (TLR) signaling. CrownEntities:
Keywords: acute myeloid leukemia; cancer differentiation; cardiolipin; leukemia initiating cell; mitochondria; phosphatidylserine; phospholipids; tafazzin
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Year: 2019 PMID： 30930145 PMCID： PMC7137093 DOI： 10.1016/j.stem.2019.02.020
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633