Grant: CIHR Fellowship

Myelodysplastic syndrome is the most common form of blood cancer, with an estimated 60,000 to 120,000 cases in the United States. Sufferers of MDS have imbalances in their kinds of blood cells, eventually leading to bone marrow failure, or a more rapid and deadly blood cancer. There are no drugs which cure MDS, but one drug, azacytidine, helps alleviate symptoms in about two thirds of patients. Nevertheless, even among those patients for whom azacytidine is effective, the disease eventually becomes resistant. Evidence suggests that MDS originates among blood-producing stem cells in the bone marrow gone wrong. We are able to sort out those stem cells from bone marrow samples, and examine each cell's DNA methylation (a kind of molecular switch which controls the cell). Many cancers disruptiively increase DNA methylation to turn off anti-cancer genes. Azacytidine does the opposite and decreases DNA methylation and decreases DNA methylation effect -- it decreases DNA methylation, and, it is believed, switches anti-cancer genes back on. By examining DNA methylation in cells from patients who were responsive to azacytidine and comparing it with those who became resistant, we hope to uncover the mechanism of azacytidine resistance. This could quickly lead to new or complimentary therapies which would help patients to live longer, and with better quality of life.