Validated Critical Roles of Bruton’s Tyrosine Kinase (BTK) in Chronic Lymphocytic Leukemia (CLL)

Abstract

Chronic lymphocytic leukemia (CLL) is a type of blood cancer with accumulated abnormal B cells growing out of control in bone marrow, blood and secondary lymphoid organs. It is the most common adult leukemia in the western world and remains incurable . Identification of therapeutic targets and development of effective target therapies are crucial and highly demanding. The well tolerated Bruton’s tyrosine Kinase (BTK) inhibitor, ibrutinib (formally called PCI-32765) , represents one of the most exciting breakthroughs in the field of B cell malignancy therapy. In clinical investigation ibrutinib has been shown to have significant clinical activity against B cell malignancies including CLL and it was recently approved for the treatment of mantle cell lymphoma and CLL . BTK is a critical component of the B cell receptor (BCR) signaling pathway . Beside BTK, other kinases such as IL2-inducible T-cell kinase (ITK) have been identified as targets of ibrutinib . The lack of selectivity of ibrutinib makes it necessary to validate the critical role of BTK in CLL. In a recent study , Woyach and colleagues confirmed the critical function of BTK in the initiation and expansion of CLL and validated BTK as an important target of ibrutinib.