Research Abstracts Online
January 2009 - March 2010
University of Minnesota Twin Cities
College of Biological Sciences
Department of Genetics, Cell Biology, and Development
PI: Brian G. Van Ness
Integrated Pharmacogenomic Modeling of Myeloma
Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow that affects approximately 20,580 new patients each year. Symptoms of this disease are often incredibly painful: bone lesions, anemia, immunodeficiency, renal failure, and hypercalcemia are common. The patients have a median age of 71, making MM primarily a disease of the elderly. Currently, there is no cure for MM, and major chemotherapeutic treatments over time have included dexamethasone, melphalan, and bortezomib (Velcade).
To identify genetic, phenotypic, and genomic profiles that impact therapeutic responses in myeloma, in vitro cell lines established from myc x bcl-xL double transgenic mice are treated with dexamethasone, melphalan, and several proteasome inhibitors. Gene expression profiles are then examined to identify differential expression of genes with respect to sensitivity of each drug. Analytical approaches are taken to develop an intersection of genetic, phenotypic, and genomic predictors of drug response that will have applications to assessment of clinical trials. Ultimately, integrated pharmacogenomic profiling may become an essential tool for individualizing the most efficacious multiple myeloma treatment.
Tzu Greg Wu, Research Associate