Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia

摘要: Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells that depend on host factors in the tissue microenvironment for survival and proliferation. In vitro, CLL rapidly undergo apoptosis unless microenvironmental are provided support their survival. Signaling pathways activated vivo include B-cell receptor (BCR) NF-κB pathways. Thus, disease “addicted to host” dependent promote normal development, expansion, survival; this particularly true case BCR signaling cascade. Small-molecule inhibitors kinases essential signal transduction abrogate stimulating effects cells. The orally administered tyrosine kinase fostamatinib ibrutinib phosphatidylinositol 3-kinase inhibitor GS-1101 have induced impressive responses relapsed refractory patients, mostly with moderate side effects. Reductions lymphadenopathy splenomegaly seen within weeks frequently accompanied by transient rise absolute lymphocyte count asymptomatic probably result changes cell trafficking. This review discusses biologic basis as targeted therapy summarizes exciting early clinical experience these agents.