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Multiple myeloma (MM) is the second most common type of cancer where cancer cells accumulate in the bone marrow, crowding out healthy blood cells. Studies at the National Cancer Institute of Singapore (CSI Singapore) and the Cancer Institute of Singapore (CSI Singapore) have uncovered an association between RNA abnormalities and MM progression. In particular, the team discovered that overexpression of ADAR1, has an RNA-editing enzyme, and a modified gene caused by irregular RNA editing to key progression and progression of resistance to current treatments.
Survival rates for MM patients have significantly improved over the years. However, about 10 to 15 per cent continue to be low-risk patients with low survival rates, as they develop resistance to drug treatments.
Research on MM in the last decade was mainly aimed at understanding how DNA misunderstandings contribute to the development of MM. More recently, RNA abnormalities have been found to be associated with different cancers such as gastric cancer and liver cancer. As such, the team at CSI Singapore embarked on the study of the biological implications of RNA defects on the progression of MM.
The team 's analysis revealed that the MM RNA exists in an abnormally modified state, which is why MM supports progression in two ways. The first is an abnormally elevated level of ADAR1 expression in myeloma cancer cells. This overexpression of ADAR1 causes myeloma cancer cells to become stronger. The second is the irregular RNA editing of NEIL1, a gene associated with lung carcinoma and colorectal cancer. NEIL1-edited myeloma cancer cells show more cancerous nature where they lose the ability to repair DNA damage and show increased resistance to a standard MM drug. Collectively, patients with high ADAR1 expression and compromised NEIL1 function were found to be responsive to the available treatments for MM.
CSI Singapore is a well-known group of drugs, known as DSB-inducing agents, which can be used to inhibit NEIL-edited cells, opening the door to new, effective treatment options for high-risk MM patients .
Professor Chng Wee Joo, Deputy Director and Senior Principal Investigator at CSI Singapore, who led the study, said, "Our study has shown that RNA defects are both clinically and biologically relevant in MM, and by exploring these RNA abnormalities further, we may unravel more novel insights on MM molecular pathogenesis Each piece of new knowledge is derived from the theory of MM biology, paving the way for the development of innovative therapeutics patients. "
The study was published in scientific journal, Blood, in September 2018.
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Materials provided by National University of Singapore. Note: Content can be edited for style and length.
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