Research progress in targeted therapies of chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is one of small B-cell lymphomas and leukemias, characterized as a clonal disease of mature B cells. The disease is remarkably heterogeneous, with the majority of patients having an indolent course, yet they are currently incurable. Abnormal signaling pathways are indispensable in the pathogenesis of CLL. In CLL, the common abnormalities of signaling pathways include B-cell receptor (BCR) signaling, apoptosis, nuclear factor kappa B (NF-κB) signaling and Notch signaling. According to the target in signaling pathways, a series of targeted drugs, such as Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, zanubrutinib), phosphorylate phosphoinositide 3-kinase (PI3K) inhibitor (duvelisib) and B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax), which have significantly changed the prognosis of patients in clinic. Other targeted drugs, such as fenebrutinib, nemtabrutinib and umbralisib, as well as chimeric antigen receptor T-cell (CAR-T) therapy developed in the field of immuno-oncology and T cell engineering, are currently under trial, with more personalized treatment modalities being explored, which may become potential drug targets in the future. In this paper, relevant literature of CLL was reviewed, and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

Keywords

• chronic lymphocytic leukemia (cll)
• molecular pathogenesis
• targeted therapy
• chimeric antigen receptor t-cell (car-t) therapy