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Chronic lymphocytic leukemia (CLL) is the most frequent, yet by conventional therapy still incurable, leukemia in the Western world. Accumulating evidence of the role of B  cell receptor (BCR) pathway in CLL B  cell bio-logy suggests the possible use of BCR inhibitors for targeted therapy. Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS 1101) targeting BCRassociated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL. These findings will likely modify treatment approaches for chronic lymphocytic leukemia and some other B  cell lymphomas in the near future. Herein, we review the data on BCR pathway deregulation in malignant CLL B  cells, and the results of clinical trials utilizing fosfamatinib, ibrutinib and GS 1101.

Inhibition of B Cell Receptor Signaling: A First Targeted Th erapeutic Approach for Chronic Lymphocytic Leukemia and Other B Cell Lymphomas