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 β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse mode...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2009-03, Vol.113 (12), p.2791-2794
Main Authors: Holler, Claudia, Piñón, Josefina D., Denk, Ursula, Heyder, Christoph, Hofbauer, Sebastian, Greil, Richard, Egle, Alexander
Format: Article
Language:English
Subjects:
Biological and medical sciences
Hematologic and hematopoietic diseases
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKCβ in the development of murine CLL. TCL1 overexpression did restore the CD5+ B-cell population that is absent in PKCβ-deficient mice. However, PKCβ-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCβ in the establishment of the malignant clone. Moreover, targeting of PKCβ with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKCβ may be a relevant target for the treatment of CLL.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-06-160713