Retinoid-mediated signaling pathways in CD38 antigen expression in myeloidleukemia cells

The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional prot ein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellula r calcium from ryanodine-sensitive intracellular pools. By virtue of its ab ility to synthesize cADPR as well as to act as an adhesion and signal trans duction molecule, CD38 may play a role in such diverse physiological proces ses as cell growth, apoptosis, differentiation, and inflammation. Equally i nteresting is the pattern of CD38 expression in hematopoeitic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whe reas mature circulating blood cells lack or express very low levels. The ex pression is also high on malignant hematopoeitic cells and thus may be of p rognostic relevance in certain leukemias. Presently, there is little inform ation available on the factors that regulate the expression of CD38 antigen in hematopoeitic cells. In this review, we summarize recent findings on th e regulation of CD38 antigen by retinoids (vitamin A and related compounds) . At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induc ed expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor.