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. Seneviratne et al. performed a CRISPR screen and identified tafazzin (TAZ) as important for the growth of leukemia cells. The inhibition of TAZ specifically reduced the stemness of leukemia cells by increasing phosphatidylserine levels and activating toll-like receptor signaling.
Original language | English (US) |
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Pages (from-to) | 621-636.e16 |
Journal | Cell stem cell |
Volume | 24 |
Issue number | 4 |
DOIs | |
State | Published - Apr 4 2019 |
Keywords
- acute myeloid leukemia
- cancer differentiation
- cardiolipin
- leukemia initiating cell
- mitochondria
- phosphatidylserine
- phospholipids
- tafazzin
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Cell Biology