Grant: Doctoral Research Award: Canada Graduate Scholarships

Myelodysplastic syndromes (MDS) are cancers originating from the blood-forming cells present in the bone marrow. In MDS, the disease either results in a failure to produce enough blood cells to survive or in 20% - 40% of the patients, the disease progresses to a very aggressive leukemia. Currently, only a bone marrow transplant can cure a patient. However, not all patients are eligible for a marrow transplant. For such patients, the only standard therapy is the use of a drug called Azacitidine (AZA). In MDS, chemical changes to the DNA called DNA methylation, is commonly observed. AZA reverses this DNA methylation changes. However, 50% of the patients do not respond to the AZA. It is yet unknown why some patients respond to AZA while others don't, in other words are resistant to AZA. Currently, there are no further treatment options for such patients, raising the pressing need to understand how AZA resistance develops. In the bone marrow of an MDS patient, certain rare cells are responsible for the initiation and progression of MDS. These rare cells also known as the MDS-stem cells can give rise to more MDS-stem cells as well as mature cancerous cells which then fill up the patient's bone marrow. Previous studies have shown that treatment with AZA only kills the more mature cancerous cells but not the MDS-stem cells themselves . Thus, to understand how resistance to AZA develops, we need to understand the nature of these MDS-stem cells. This project focusses on studying these rare MDS-stem cells from patients who are responsive and non-responsive to AZA. Through this project I want to identify which type of blood cell becomes the MDS-stem cell and examine if the nature of the identified MDS-stem cells in AZA responders is different from the non-responders. Understanding the nature of these stem cells will help identify new therapies that can be used along with AZA to target these stem cells and improve the outcomes of AZA non-responsive patients.