Pioneering Discovery: Enzyme Linked to Leukemia Spread Unveiled by Scientists

A group of researchers has discovered an unexpected role played by ELOVL6, an enzyme involved in lipid metabolism, in the development and survival rates of acute myeloid leukemia patients. This finding could potentially make ELOVL6 a target for future leukemia treatments.

The research team from the University of Tsukuba has found an unanticipated correlation between the enzyme ELOVL6, which has a crucial role in lipid metabolism, and the growth of leukemia.

Lipids, organic fatty compounds present in vast diversity within cells, undergo lipid metabolism – a process of creation and breakdown crucial for cell composition, functionality, and membrane operation. An integral enzyme in this process is ELOVL6, which elongates fatty acid chains and plays a key part in various cellular metabolic processes.

Nevertheless, the correlation between lipid metabolism and blood production, including blood-related disorders, remains largely uncharted territory in scientific research. To bridge this knowledge gap, the Tsukuba researchers have elucidated a significant role of ELOVL6 in the development of acute myeloid leukemia (AML), a type of blood cancer. This role is performed through a pathway regulating cell movement, and the research also found that elevated levels of ELOVL6 correlate with lower survival rates among leukemia patients.

The researchers found that eliminating ELOVL6 in bone marrow stem cells – the origin of all types of blood cells – changed cellular lipid contents and hindered engraftment in mice, a process where transplanted stem cells migrate through the blood to the bone marrow.

Significantly, the absence of ELOVL6 also stopped the development of leukemia in a mouse model. Gene expression profile analysis revealed that cells without ELOVL6 showed modifications to genes involved in cytoskeletal remodeling and chemotaxis – mechanisms governing cell movement. Subsequent in-depth molecular studies confirmed that the lack of ELOVL6 impaired cytoskeletal remodeling and chemotaxis, probably through malfunction of PI3K and Rac1, essential cellular regulatory molecules.

Professor Shigeru Chiba, the senior author of the study, explains, “Minor changes in cell membrane lipid content can have unexpected and dramatic impacts on blood cancer development.” Interestingly, while the production of blood and AML pathology are closely connected, the absence of ELOVL6 did not influence normal blood production or function.

Using data from online databases, the team discovered a correlation between high ELOVL6 levels and poor survival rates from AML. “The possible targeting of ELOVL6 and its downstream pathways for leukemia treatment was previously unconsidered, as this link between lipids and blood function was uncharted,” explains Professor Chiba.

However, this study now reveals that ELOVL6 and its associated pathways could be promising targets for innovative leukemia treatments. This discovery is likely to spur further research into the relationship between lipid metabolism and cancer.

This research was funded by 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.

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More about Leukemia and ELOVL6 enzyme

• University of Tsukuba
• Information on Acute Myeloid Leukemia (AML)
• Overview of Lipid Metabolism
• Understanding the Role of Enzymes
• Understanding Leukemia Therapies
• The Role of ELOVL6 in Metabolism