“Normal blood-forming cells respond to signals from the environment, such as stress, inflammation or infection,” said Stephen D. Nimer, M.D., Director of Sylvester, and professor of medicine, biochemistry and molecular biology. “However, that signaling pathway is subverted in cancer cells, which continue to grow, endangering vital organs and systems.”
In a study published in the Journal of Clinical Investigation, Nimer and his research team found that the enzyme PRMT5 is essential for hematopoiesis, the formation of blood cell components. Using an experimental genetic model, he found that removal of PRMT5 halted the production of blood cells in adult mice.
“Growing evidence has indicated a critical role of the enzyme PRMT5 in the development of leukemia, lymphomas and other types of cancers, such as lung and ovarian cancer,” Nimer said. “This makes it an attractive therapeutic target in these diseases. Our new study suggests that drugs to inhibit PRMT5 could be used in a combination with other medications that block growth signals in new non-chemotherapeutic strategies.”
Nimer’s co-authors from Sylvester on the article describing this work, “Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis,” were Fan Liu, Ph.D., assistant professor of biochemistry and molecular biology, Guoyan Cheng, Ph.D., post-doctoral associate, Pierre-Jacques Hamard, Ph.D., associate scientist, Sarah Greenblatt, Ph.D., post-doctoral fellow, Lan Wang, Ph.D., member of Sylvester and assistant professor of biochemistry and molecular biology, Na Man, Ph.D., senior research associate, Madhavi Tadi, M.Sc., senior research associate, and Luisa Luciani, Ph.D., former post-doctoral associate. Two other contributors were from Memorial Sloan Kettering Cancer Center in New York City.
Nimer’s study of PRMT5 expands on his previous research on how to develop epigenetic-focused therapies for cancer patients. “In a normal person, stopping the hematopoiesis process could have serious clinical consequences,” Nimer said. “But in many leukemia patients, the malfunctioning blood-producing cells in the bone marrow need to be eliminated as part of the treatment process.”
University of Miami