Grant: Operating Grant

Leukemia and lymphoma (T cell malignancies) are among the fastest rising cancers in North America. For example, acute T lymphoblastic leukemia (T-ALL) accounts for approximately 15% of all childhood leukemia and for 25 % of all adult leukemia. The cellular and molecular mechanisms that promote the development of these cancers are not well understood. Furthermore, their treatment with chemotherapy is limited because of the development of drug resistance. Therefore, it is critical to investigate the mechanisms/strategies used by malignant T cell leukemia/lymphoma to progress and resist the action of chemotherapeutic drugs. In this context, we have identified that certain cell surface molecules called integrins that are expressed by T-ALL cancer cells can promote their growth and protect them from the action of chemotherapy. We thus want to investigate how these cell surface receptors function to promote the malignancy, and the resistance to chemotherapy of T cell leukemia. The proposed studies will involve clinical samples from patients with T-ALL and the use of animal models of T cell leukemia. Findings from these studies are likely to further our understanding on how T-ALL cancer cells develop. In addition, our studies may lead to the discovery of novel therapeutic strategies and to the identification of novel biomarkers, which can predict the therapeutic response and clinical outcome of T-ALL patients.