Scientists have discovered that an enzyme involved in lipid metabolism may play a significant role in acute myeloid leukaemia (AML).
Lipids form a key part of the cell membrane, and so lipid metabolism plays a crucial part in the function of cells. Although it is known that lipid metabolism has a role in cancer cell functions, little research to date has been carried out.
A research team led by Professor Shigeru Chiba of the University of Tsukuba, Japan, looked at how lipid metabolism enzymes might be involved in leukaemia development. Their studies led them to study the enzyme ELOVL6, which helps create long-chain fatty acids.
A high expression of ELOVL6 has previously been linked to poor prognosis of patients with breast and liver cancer, the researchers say. The team analysed data from the Cancer Genome Atlas cohort, and again showed an association between high ELOVL6 expression levels and worse overall survival in AML.
In studies with mice, deletion of the Elovl6 gene prevented the engraftment of AML cells in the bone marrow, and so prevented the progression of the disease. Further analysis of gene activity in cells lacking ELOVL6 showed these cells had alterations to genes involved in cytoskeletal remodelling and chemotaxis – key components of the machinery involved in cell movement
In the journal Leukemia, the authors report: “Our finding that ELOVL6 loss hampers acute myeloid leukaemia propagation will facilitate the development of novel cancer treatments.”
Professor Chiba said: “Taken together, this indicates that relatively small changes to the cell membrane lipid content can have unforeseen and drastic effects on the development of blood cancers.
“ELOVL6 and its downstream pathways had never before been considered as potential targets for leukaemia treatment.
“Now, however, this study reveals that ELOVL6 and its associated pathways are very promising targets for the development of novel therapies for leukaemia, and is expected to springboard further research into the relationships between lipid metabolism and cancer.”
Source:
Kiyoki Y, Kato T, Kito S, Matsuzaka T, Morioka S, Sasaki J, Makishima K, Sakamoto T, Nishikii H, Obara N, Sakata-Yanagimoto M, Sasaki T, Shimano H, Chiba S. (2023) “The fatty acid elongase Elovl6 is crucial for hematopoietic stem cell engraftment and leukemia propagation.” Leukemia, doi: 10.1038/s41375-023-01842-y
Link: https://www.nature.com/articles/s41375-023-01842-y
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