PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia

The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C beta (PKC beta) is an essential signaling element of the BCR and was recently shown to be over-expressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKC beta in the development of murine CLL. TCL1 overexpression did restore the CD5(+) B-cell population that is absent in PKC beta-deficient mice. However, PKC beta-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKC beta in the establishment of the malignant clone. Moreover, targeting of PKC beta with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKC beta may be a relevant target for the treatment of CLL. (Blood. 2009;113:2791-2794)