PKC-d (protein kinase C-d) was announced as a promising new target in chronic lymphocytic leukemia (CLL) treatment

06-15-2006

Recent studies from University of California, San Francisco add to knowledge base.

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Study 1: PKC-d (protein kinase C-d) was announced as a promising new target in chronic lymphocytic leukemia (CLL) treatment.

"Constitutively activated signaling pathways contribute to the apoptosis-defect of B-CLL cells. Protein kinase C-d is a permanently activated kinase and a putative downstream target of phosphatidylinositol-3 kinase in B-CLL," researchers in the United States reported.

"Blockade of PKC-d by the highly specific inhibitor rottlerin induces apoptosis in chronic lymphocytic leukaemia (CLL) cells," explained I. Ringshausen and colleagues, University of California, San Francisco. "By co-culturing bone marrow stromal and CLL cells, we determined that the proapoptotic effect of rottlerin is not abolished in the presence of survival factors, indicating that a targeted therapy against PKC-d might be a powerful approach for the treatment of CLL patients. The downstream events following rottlerin treatment engage mitochondrial and non-mitochondrial pathways and ultimately activate caspases that execute the apoptotic cell death.

"Herein we report that the inhibition of PKC-d decreases the expression of the important antiapoptotic proteins Mcl-1 and XIAP accompanied by a loss of the mitochondrial membrane potential Delta psi. In addition, we discovered that ZAP-70-expressing cells are significantly more susceptible to rottlerin-induced cell death than ZAP-70 negative cells. We finally observed that rottlerin can augment cell toxicity induced by standard chemotherapeutic drugs."

The researchers concluded, "Conclusively, PKC-d is a promising new target in the combat against CLL."

Ringshausen and colleagues published their study in Leukemia (Mechanisms of apoptosis-induction by rottlerin: therapeutic implications for B-CLL. Leukemia, 2006;20(3):514-520).

For additional information, contact I. Ringshausen, University of California, San Francisco, Center Comprehensive Cancer, Box 0-875, 2340 Sutter St., San Francisco, CA 94115, USA.

This article was prepared by Pharma Business Week editors from staff and other reports. Copyright 2006, Pharma Business Week via NewsRx.com.