Researchers found that hypomethylating agents, a medication commonly used to treat myelodysplastic syndrome, could “turn on” the gene that causes cancer,
Hypomethylating agents (HMA) are currently used as a first-line treatment for individuals with myelodysplastic syndrome (MDS), a group of conditions where there is an inadequate generation of healthy mature blood cells in the bone marrow. However, the exact mechanism through which HMAs work is still unknown. Although this has not yet been completely proved, one possible concern is that they could activate a sleeping oncogene.
In a recent study, researchers from the National University of Singapore’s (NUS) Cancer Science Institute of Singapore (CSI Singapore) in close cooperation with Boston’s Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS) have shown that HMAs can and do activate the oncofetal protein SALL4.
The research was published in the academic journal New England Journal of Medicine and was also carried out in partnership with the University of Tor Vergata in Rome, Italy, and the Institute of Hematology and Blood Diseases Hospital in Tianjin, China.
Turning on the gene that causes cancer
SALL4 is a known oncogene, and the expression of SALL4 has been found to contribute to the development of MDS and leukemia. A study conducted by another research group in 2016 demonstrated that SALL4 activation in a liver cancer cell line was associated with hypomethylation.
Professor Daniel Tenen from CSI Singapore and his team demonstrated in 2021 that hepatitis B virus induced SALL4 demethylation in liver cancer through an RNA mediated mechanism. To examine possible upregulation of oncogenes in patients being treated with hypomethylating agents, Professor Tenen’s team collaborated with the other groups to study the association between HMA utilized and SALL4 activation, as well as the implications on survival outcomes. READ MORE...
