Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Cancer cells are hard to eradicate. A key reason is their dissemination through the body. This can be well illustrated in the case of B cell leukemia (white blood cancer), which comprises the most common type of childhood cancer and the most prevalent leukemia in adults. Leukemic cells from these diseases spread themselves by migration into different destinations of the body such as bone marrow and lymph nodes. Cells residing in these locations find microenvironments that favor their survival and growth and protect them from being killed by chemotherapy drugs now generally used in the clinic. Thus, interfering with the migration and localization of leukemic cells may provide new opportunities to block their dissemination and expansion and to disrupt their resistance to conventional chemotherapy. TAPP proteins are components of a molecular signaling pathway frequently activated in cancer cells. Recent work in our lab has found an interesting correlation of TAPP protein expression with a more aggressive, highly migratory subset of leukemic cells. The hypothesis of the proposed research is that TAPP proteins are key mediators of leukemic cell migration. This work will apply genetic and pharmaceutical approaches to inhibiting TAPP function and examine the effect on the migration and dissemination of leukemic cells in vitro and in vivo. My preliminary discovery is that genetic depletion of TAPP proteins leads to impaired migration capacity of a leukemic cell line in vitro. Expectations on the future work are that inhibition of TAPP function in leukemic cells may block their dissemination in vivo, limit their expansion, render them susceptible to chemotherapy killing and improve host survival. This research may therefore potentially identify new therapeutic intervention targets for B cell leukemia leading to more effective treatment of these malignant diseases and thus significantly contribute to Canadian public health.