Telomerase Inhibition Promotes Recovery of Red Blood Cells in MDS

Andrew M. Brunner, MD, assistant professor of medicine at Harvard Medical School and at the Center for Leukemia at Massachusetts General Hospital in Boston, Massachusetts, discusses the mechanism of action of telomerase inhibitors as treatment for anemia related to myelodysplastic syndrome (MDS).

According to Brunner, mutations in MDS progenitor cells cause impaired production of red blood cells, and emerging research is showing the role of telomerase in causing anemia and dependence on red blood cell transfusions in patients with MDS.

Using a telomerase inhibitor such as imetelstat (Rytelo) has been shown to selectively deplete mutated MDS stem cells relative to healthy bone marrow cells. This leads to recovery of the bone marrow and improvements in red blood cell counts in these patients. Brunner says promoting healthy progenitor cells and decreasing malignant cells can reduce the need for transfusions and improve outcomes for patients with lower-risk MDS whose anemia doesn’t respond to erythropoiesis-stimulating agents.

TRANSCRIPTION

0:10 | I think that what we're learning is that there are many ways in which mutant MDS progenitor cells are impaired in their ability to produce red cells. This is still kind of an emerging area of work, trying to understand how telomerase is important in not only the persistence of these cells, but then in the development of red cell transfusion dependence.

0:40 | It does seem to be that stem cells that have mutations in a number of MDS genes are more dependent on telomerase being functional, and that when you subsequently give a telomerase inhibitor that may deplete those cells relative to other healthy cells in the bone marrow. So, then you get recovery of the bone marrow, some healthy hematopoiesis, and a relative decrease in malignant hematopoiesis. So, we think that by doing this, we may be able to shift red blood cell and other blood production back to healthier progenitors by selectively depleting these really telomerase-dependent mutant cells.