Scientists at the University of Tsukuba have made a groundbreaking discovery that could potentially lead to new therapies for leukemia. They have found a connection between an enzyme called ELOVL6, which plays a role in lipid metabolism, and the development of acute myeloid leukemia (AML). The researchers have also found that higher levels of ELOVL6 are linked to reduced survival rates in leukemia patients.
Lipid metabolism is a fundamental process in cells that regulates cellular composition and functionality. ELOVL6, a key enzyme in this process, is involved in various cellular metabolic processes. However, its connection to the development of blood disorders, including leukemia, has not been extensively studied.
To explore this link, the team deleted ELOVL6 in bone marrow stem cells, which are responsible for producing blood cells. They found that the deletion of ELOVL6 altered cellular lipid contents and inhibited the engraftment of these stem cells in mice. Engraftment is a crucial process in which transplanted stem cells travel through the blood to the bone marrow. Importantly, the loss of ELOVL6 also prevented the development of leukemia in a mouse model.
Further analysis revealed that the cells lacking ELOVL6 had alterations to genes involved in cell movement. This impairment of cell movement was linked to dysfunction of PI3K and Rac1, which are vital cellular regulatory molecules. The researchers concluded that even small changes to the cell membrane lipid content can have significant effects on the development of blood cancers.
The team also found a correlation between high levels of ELOVL6 and worse overall survival in AML patients. This discovery opens up new possibilities for the development of targeted therapies for leukemia. The researchers believe that ELOVL6 and its associated pathways could be promising targets for future leukemia treatments.
Senior author Professor Shigeru Chiba explained, “This link between lipids and blood function was unexplored, and ELOVL6 and its downstream pathways had never before been considered as potential targets for leukemia treatment. This study reveals their potential and will inspire further research in the field of lipid metabolism and cancer.”
The study, titled “The fatty acid elongase Elovl6 is crucial for hematopoietic stem cell engraftment and leukemia propagation,” was published in the journal Leukemia on March 8, 2023. The research was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the SENSHIN Medical Research Foundation, the Takeda Science Foundation, AMED, and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED.