Leukemia genesis is a stepwise process, and events leading to leukemic cell progression include mutations of key signaling proteins and epigenetic changes of gene expression patterns. The overall behavior of any given leukemic cell is therefore the sum of epi-genetic, genetic and microenvironmental influences. Ultimately, these influences converge to protein function and cell signaling properties. Thus, differences in leukemic cell behaviors and heterogeneity of cancer cell responses to therapy can be thought of as reflecting the signaling differences in leukemic cells. Among the signaling pathways involved in B-cell biology that may be dysregulated in B-CLL cells, thus impacting leukemic cell behaviors, the BCR signaling network appears to have a fundamental role. Gaining deeper insights into the role of BCR signaling in B-CLL pathophysiological mechanisms may lead to the identification of biomarkers for disease progression and responsiveness to therapy, and to interference with BCR signaling elements that are crucial for B-CLL, moving from population-based approaches toward personalized medicine.
Expert Rev Hematol. 2012;5(3):341-348. © 2012 Expert Reviews Ltd.