Grant: Project Grant

Multiple Myeloma (MM) is a type of blood cancer newly diagnosed in >2000 Canadians each year. MM cells carry many mutations in their DNA, which indicates that these cells may suffer from a process known as genome instability. The causes of this instability are not known, but finding them would help us design better therapies for MM. Roughly 11% of MM cases have defects in a gene called DIS3, and these defects occur more often in the most lethal nonhyperdiploid form of the disease. We have evidence that these defects can lead to high numbers of mutations by inducing instability; to our knowledge, our research is the first to link defects in DIS3 with this mutation-inducing process. The proposed research project will confirm and extend our understanding of this mechanism of genome instability in DIS3-deficient cells. Using this knowledge, we will attempt to both predict and design new therapeutic approaches to selectively kill DIS3-deficient MM cells. These direct tests and new mechanistic understanding will open new avenues for designing therapies that are effective in individuals with DIS3-deficient MM.