Role of CD38 Expression in Diagnosis and Pathogenesis of Chronic Lymphocytic Leukemia and Its Potential as Therapeutic Target

CD38 is widely accepted as a marker for unfavorable prognosis in chronic lymphocytic leukemia (CLL). Nevertheless, its direct contribution to the disease pathogenesis is not very well understood. Recent data indicate that CD38 may promote CLL pathogenesis by enhancing proliferation in synergy with B-cell receptor (BCR) signaling and by supporting migration and homing of CLL cells to secondary lymphoid organs, where the malignant cells receive support from the tumor microenvironment. CD38 may also contribute to a suppressed anticancer immune response through the production of tolerogenic compounds. This review first shortly summarizes the biology, expression, and function of CD38 in general and in CLL cells in more detail. Next, the current literature and open questions regarding a direct contribution of CD38 to CLL pathogenesis are critically reviewed. Finally, I discuss the potential of CD38 as therapeutic target in light of its possible roles in CLL and the promising results of clinical trials with CD38 antibodies in multiple myeloma (MM).