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Targeted agent shows promise for chronic lymphoid leukemia
Date:9/13/2010

essential for survival of cells generally. This made it an unsuitable target for small molecule inhibitors until recently when research showed that PI3K-delta expression occurs mainly in hematopoietic cell types. Preclinical studies suggest that blocking this molecule may kill B cells with little toxicity to other hematopoietic cells.

The present study, which used CLL cells from patients, found the following:

  • CLL cells show high PI3K pathway activity and PI3K-delta expression;
  • CAL-101 preferentially kills CLL cells compared to normal B-cells;
  • CAL-101 selectively inhibits PI3K-delta and directly promotes apoptosis in primary CLL cells, and it disrupts multiple external survival pathways;
  • CAL-101 cell killing is caspase dependent and not diminished by the presence of stromal cells;
  • CAL-101 does not kill normal T-cells or NK cells or reduce antibody-dependent cellular cytotoxicity, but it does lower production of inflammatory and anti-apoptotic cytokines by activated T-cells.


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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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