A new study led by Princess Margaret (PM) Cancer Centre Research Director Dr. Aaron Schimmer suggests that an increase in a certain class of fats, known as phospholipids, plays a fundamental role in the initiation and growth of acute myeloid leukemia (AML)—an aggressive form of blood cancer.
Phospholipids have many important roles in the body, including storing energy, relaying messages and serving as the building blocks of life. Because of this, changes in these fat-like substances are linked to a number of diseases, including cancer.
Dr. Schimmer and his team found that loss of a protein known as Taffazin (TAZ) increased levels of the phospholipid phosphatidylserine and decreased the growth and survival of specific AML cells that are known to initiate and maintain disease. Interestingly, their experiments showed that loss of TAZ had no effects on healthy blood cells.
“These findings shed new light on the impact that phospholipids have on leukemia initiation and progression,” says Dr. Schimmer. “Finding ways to change the composition of these molecules in the body may represent a new way to block the development or progression of AML.”
This work was supported by the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, the Government of Ontario, the National Institutes of Health, the University of Toronto, the PM Cancer Centre, the Lady Tata Memorial Trust and The Princess Margaret Cancer Foundation. Dr. Schimmer holds the Barbara Baker Chair in Leukemia and Related Diseases.
Seneviratne AK, Xu M, Aristizabal Henao JJ, Fajardo VA, Hao Z, Voisin V, Wei Xu G, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, Sharon D, Thomas G, Chouinard-Watkins R, Hawley JR, Schafer C, Yau HL, Khuchua Z, Aman A, Al-awar R, Gross A, Claypool SM, Bazinet R, Lupien M, Chan S, De Carvalho DD, Minden MD, Bader GD, Stark KD, LeBlanc P, Schimmer AD. The mitochondrial transacylase, Tafazzin, regulates for AML stemness by modulating intracellular levels of phospholipids. Cell Stem Cell. 2019 March 28. doi: 10.1016/j.stem.2019.02.020.