B-CLL has long been regarded as a disease of accumulation rather than proliferation. However, evidence from in vivo labeling experiments and analysis of telomeres 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. 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. However, further cell cycle progression may require additional costimulatory signals (i.e., IL-4 and CD40L) provided by bystander cells in B-CLL microenvironments. 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, thus confirming an important role for ERK in B-CLL pathogenesis.
Expert Rev Hematol. 2012;5(3):341-348. © 2012 Expert Reviews Ltd.