Project Title: Differential Gene Expression in CLL Cells
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Principal
Investigator:
Shantaram S. Joshi, Ph.D. Professor,
Department of Genetics, Cell Biol. and Anatomy,
Co-Investigators:
R. Gregory Bociek, M.D. Associate
Professor, Section of Oncology and Hematology,
Philip J. Bierman, M.D., Associate
Professor, Section of Oncology and Hematology,
Dennis D. Weisenburger, M.D., Professor,
Department of Pathology and Microbiology,
University of
Abstract
Chronic
Lymphocytic Leukemia or CLL is the most common adult leukemia in the western
world with a heterogenous clinical outcome. Despite years of research, there remains
no curative treatment. CLL consists
of an abnormal expansion of malignant B cells in the bone marrow, lymph nodes,
and blood. Recently, there have
been a number of advances that have led to the identification of several factors
that predict the rate of tumor progression, treatment response, and overall
survival. Most studies of CLL have involved CLL cells isolated from the blood
since these cells are a readily accessible homogeneous population of tumor
cells. Despite the identification
of different prognostic groups, the molecular basis for these differences
remains unknown. One possible explanation is that tumor cells isolated from the
blood may represent more differentiated or mature B cells that share many of the
same properties regardless of the overall aggressiveness of the disease. In this proposal, we hypothesize that
the CLL cells in the lymph nodes clustered together in groups called
pseudofollicles, or CLL cells in the bone marrow, may play a significant role in
determining the aggressiveness of a leukemia in a given patient. Therefore, we will compare the gene
expression of CLL cells in the bone marrow/lymph nodes with CLL cells in the
blood from the same patients. Thus, the results of these studies might provide
us with data that will help us better predict the clinical outcome in CLL
patients.