Bettine Gibbs Butler University
Faculty Sponsor(s): Chioniso Patience Masamha Butler UniversityMantle Cell Lymphoma (MCL) is an aggressive malignancy that accounts for 6-10% of non-Hodgkin lymphomas. MCL is considered clinically incurable upon relapse, rendering an unfavorable prognosis. Hence, it is imperative to identify novel therapeutic strategies that effectively target deregulated pathways that contribute to MCL. The hallmark of MCL is the constitutive overexpression of the G1-phase cell cycle regulatory oncogene cyclin D1, which is not expressed in B-lymphocytes. This results in uncontrolled cell proliferation. The cyclin D1 driven proliferative phenotype is associated with poor survival in MCL patients. Uncontrolled cell proliferation results in metabolic reprogramming to support the energy and biosynthetic needs of the rapidly dividing cells. These metabolic changes include altered expression of genes involved in metabolism and result in increased glucose and glutamine uptake in tumor cells. We hypothesize that targeting both hyper-proliferation and altered cell metabolism would be more efficacious in inducing cancer cell death. Our Western blot analysis shows that MCL cells overexpress both cyclin D1 and glutaminase, the enzyme that is critical for glutamine metabolism. Treatment targeting cell proliferation alone, or metabolism alone, decreased the cell-viability of MCL cells; however, greater cytotoxic activity was observed with dual treatment. Our preliminary data suggests concurrent targeting of both metabolism and cell proliferation in MCL cells has a synergistic effect that enhances the induction of cancer cell death.
Biochemistry & Molecular Biology
When & Where
Irwin Library 3rd Floor