CD38 as a multifaceted immunotherapeutic target in CLL

CD38 is a glycoprotein expressed on chronic lymphocytic leukemia (CLL) cells, which functions to amplify B-cell receptor signaling and regulate nicotinamide adenine dinucleotide metabolism. Increased CD38 expression on CLL cells is associated with an unfavorable disease course, resulting in shorter overall survival. While the role of CD38 as a negative prognostic marker in CLL has been established for over two decades, the therapeutic benefit to be derived by patients from its inhibition has, till date remained an unresolved subject. With the development of high-affinity anti-CD38 targeting drugs, tremendous insight has been gained on which functions of CD38 are detrimental to CLL cell survival as well as the mechanisms of leukemic cell death engaged by these anti-CD38 agents. The current review attempts to resolve how the enzyamtic and receptorial functions of CD38 contribute to CLL pathogenesis, our ability to exploit these functions for immunotherapeutic effect and development of novel strategies targeting CD38.