Antagonists To Retinoid Receptors Down-Regulate Cd38 Expression And Inhibit In Vitro Differentiation Of Cord Blood Derived Cd34+Cells.

CD38, originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most well-characterized function is the ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. However, its major enzymatic activity is the hydrolysis of NAD (NADase) implicating it as the major regulator of cellular NAD levels. CD38 expression increases with commitment and differentiation. It is not clear, however, whether such changes in CD38 are merely phenotypic, or reflect an active role for CD38 in the regulation of cell differentiation. The regulation of CD38 gene expression is under the direct control of retinoid receptors (RAR). Antagonists to RAR abolish up-regulation of CD38 gene expression as well as RA induction of granulocytic differentiation down-stream of the myeloid compartment.