Research into new ways of treating Chronic Lymphocytic Leukemia is going on all the time. As no current treatments for leukemia cure all the patients treated, doctors dealing with the disease are continually looking for new ways to treat it.

Project 6 - Pharmacology

Michael R. Grever, M.D.
Ohio State University Cancer Center

John Byrd, M.D.
Ohio State University Cancer Center

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Specific Aims

Investigators of Project 6 have also moved Flavopiridol forward clinically as a highly active drug for the treatment of CLL based on rational, pharmacologically-directed translational investigation. As part of this proposal, we will continue development of flavopiridol in collaboration with Project 5, as this represents what may be the most active agent now available for CLL. Concurrently, we will continue focusing on development of OSU-03012. Each of these agents potently induces apoptosis in CLL cells and has a distinct mechanism of action, making them promising alternative treatment approaches. In addition, investigators from Project 1 have generated a transgenic mouse that develops a chronic B-cell leukemia, and we have demonstrated that this mouse model has in vitro and in vivo features very similar to those observed in human CLL. To move towards our primary goal of improving CLL therapy, we plan to study flavopiridol (in collaboration with Projects 2 and 5) and OSU-0312 (in collaboration with Projects 1 and 2) with detailed in vitro and in vivo studies that incorporate this mouse CLL model. Our specific aims include:

1. To continue development of Flavopiridol as an effective therapeutic agent for treatment in CLL
2. To develop the PDK1/Akt inhibitor, OSU-03012, for eventual clinical evaluation in CLL
3. To use the Tcl-1 transgenic mouse model of CLL as a pre-clinical tool for developing therapies