Protein kinase C-d announced as promising new target in chronic lymphocytic leukemia treatment

04-21-2006

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.

Publisher contact information for the journal Leukemia is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

Keywords: San Francisco, California, United States, Apoptosis, B CLL, Bone Marrow, Leukemia, PKC delta, Protein Kinase C, Proteins, Proteomics, Signal Transduction, Target Therapy.

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