Grant Awarded in 2011
Stephan Stilgenbauer, M.D.
University of Ulm (Germany)
We hypothesize that critical genes are targeted by mutations during the disease course and lead to particular disease characteristics. Novel methods of analyzing samples will allow us to decipher the genetic code of CLL to understand which changes are driving refractory CLL. Modern sequencing technology holds potential to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks. These insights will identify the mutational signatures associated with different disease courses of CLL. We thus hope to answer key clinical questions necessary to move CLL research forward.
Grant Awarded in 2011 while Dr. Abruzzo was at MD Anderson Cancer Center
Lynne V. Abruzzo, M.D., Ph.D.
Ohio State University
The goal of this project is to identify genes (protein-coding and microRNAs genes) that are differentially expressed in CLL cases with +12, compared to cases with 13q- and those with no abnormalities. The information gathered may identify biological targets that contribute to the more aggressive clinical behavior of +12 and may form the basis for future individualized therapeutic approaches.
Grant Awarded in 2011
George Adrian Calin. M.D., Ph.D.
University of Texas MD Anderson Cancer Center
The purpose of this project is to decipher if miRNAs in plasma/serum (the liquid part of the blood in which cells are suspended) of CLL patients could be used as: 1) diagnostic and prognostic markers, 2) markers of response to therapy and 3) markers of residual disease or recurrence. The specific focus for this project is to determine the levels of miRNAs in the plasma/serum in large sets of CLL patients.
Plasma/serum is easily obtainable from patients for both research and clinical purposes, as it can be collected through minimally invasive blood tests. This will be the first study focusing on the identification of the clinical significance of the miRNA levels in plasma/serum in CLL patients. If successful, the study results could lead to a useful new diagnostic tool.
Grant Awarded in 2011
Ulf Klein, Ph.D.
Herbert Irving Comprehensive Cancer Center, Columbia University
There is increasing evidence that CLL cells become incapable of following the normal route of B-cell differentiation – the process of becoming a more specialized cell. It was recently found that Interferon Regulatory Factor 4 (IRF4), a gene which is part of the multistep process of normal B-cell differentiation, is associated with CLL development. We hypothesize that CLL cells fail to produce enough IRF4 needed to function normally. This subsequently arrests the CLL cells in their current developmental stage. This developmental block further exacerbates the cellular imbalance created by the loss of control of cell death and proliferation, resulting in tumor cell accumulation.
Our present proposal is aimed at understanding the biological consequences and mechanisms of reduced IRF4 expression in CLL. By deleting the IRF4 gene in mouse models, we can better understand the gene’s role in CLL cells and determine the extent to which IRF4-deletion accelerates CLL development. Clarifying the mechanisms that disrupt the normal differentiation path of the CLL cells is expected to guide the development of innovative therapeutic strategies for CLL treatment.