Signaling Pathways Activated by the B-Cell Receptor in Chronic Lymphocytic Leukemia

Maria Teresa Scupoli; Giovanni Pizzolo


Expert Rev Hematol. 2012;5(3):341-348. 

In This Article

Cell Division

B-CLL has long been regarded as a disease of accumulation rather than proliferation. However, evidence from in vivo labeling experiments[47] and analysis of telomeres[58] has revealed that B-CLL cells proliferate and die, often at appreciable levels, and that the proliferation rate is associated with disease activity and progression.[59] Although little evidence has shown direct effects of BCR stimulation on B-CLL proliferation in vitro,[42,43,59] it could be argued that BCR signaling may have a role in promoting cell cycle progression in vivo. In vitro stimulation of BCR has been shown to induce cyclin D2/CDK4 expression and G1 cell cycle progression, and these effects correlate with an unfavorable clinical course.[60] However, further cell cycle progression may require additional costimulatory signals (i.e., IL-4 and CD40L) provided by bystander cells in B-CLL microenvironments.[60] A recent report by Krysov and colleagues suggests that activation of MYK mediated by ERK may play a key role in the antigen-induced proliferation of B-CLL cells,[40] thus confirming an important role for ERK in B-CLL pathogenesis.


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