CLL microenvironment: macro important

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BlankBlood, 13 January 2011, Vol. 117, No. 2, pp. 377-378.

CLL microenvironment: macro important

W. Friedberg

UNIVERSITY OF ROCHESTER

In this issue of Blood, Herishanu and colleagues demonstrate that the lymph node

is a key site in pathogenesis of chronic lymphocytic leukemia (CLL), where

increased signaling through the B-cell receptor (BCR) contributes to

proliferation and tumor progression.1 These results have key implications in

future laboratory models of CLL, and emphasize the importance of the BCR pathway

as a therapeutic target for this disease.

BCR signaling is critical to the development and survival of B cells, and is

mediated proximally through phosphorylation of spleen tyrosine kinase (Syk), in

both normal and malignant B cells. Using small-molecule inhibitors of Syk, it

has recently been appreciated that tonic (non antigen-dependent) BCR signaling

contributes to the malignant phenotype in a subset of diffuse large B-cell

lymphoma, perhaps through activation of nuclear factor kappa B (NF(kappa) .2,3

The importance of BCR signaling—either antigen dependent or tonic—in maintaining

CLL is controversial, but recent studies have demonstrated that Syk is

overexpressed in CLL, and that pharmacologic inhibition of Syk results in

down-regulation of survival mediators and apoptosis of CLL.4

Full article

http://bloodjournal.hematologylibrary.org/cgi/content/full/117/2/377?ct=ct