Grant: Fellowship - Priority Announcement: Epigenetics

More than 7,500 Canadians suffer from B-cell lymphoma (Non-Hodgkin Lymphoma; NHL), a disease which affects particularly the lymphatic and the immune system. One subtype of NHL is the B-cell Burkitt-type lymphoma (BL), which is very aggressive and affects several tissues. In North America, this type of cancer accounts for 1-2% of all lymphoma. In Africa, BL is the most common childhood cancer. Patients with this malignancy show abnormal rearrangements in their chromosomes inducing the overexpression of the protein c-Myc. This protein is involved in cell growth and is associated with the development of several cancers. The protein Miz-1 that is under investigation in the present proposal binds to c-Myc and regulates its function. We hypothesize that Miz-1 is required for the development of BL. In our study, we will use mouse models which develop tumors similar to those observed in patients with BL. We will ablate the function of Miz-1 in these mice to verify if this protein is important for the development of the disease and whether the ablation could influence the development or progression of the disease. Since abnormal regulation of chromatin is often associated with cancer development, we will also assess the ability of Miz-1 to modulate the structure of chromatin in normal and malignant B cells. The identification of Miz-1 as an important collaborator of c-Myc in the development of BL will be an important step in the development of new, targeted therapies. In fact, if Miz-1, as our preliminary data suggest, is required for the emergence of c-Myc dependent B-cell lymphoma, it could be possible in the future to target this protein with small molecules to favor regression of these tumors in lymphoma patients.