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

Abstract

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 biology 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 BCR-associated 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.