Upregulation of CD38 gene expression in leukemic B cells by interferon types I and II

The activation antigen CD38, which has NAD(+) glycohydrolase activity in it s extracellular domain, is expressed by a large variety of cell types. Few investigations into the regulation of CD38 expression by physiologic stimul i have been reported. As the CD38 promoter contains potential binding sites for interferon (IFN) regulatory factor-1 (IRF-1), we investigated the infl uence of IFN type I (alpha and beta) and type II (gamma) on CD38 gene expre ssion of leukemic B cells. Using the IFN-responsive B cell line Eskol, we f ound by RT-PCR analysis a rapid time-dependent induction in CD38 mRNA (star ting at 6 h) with each type of IFN. This induction was independent of prote in synthesis, suggesting that CD38 gene activation does not require IRF-1 b ut is merely under direct transcriptional regulation by latent IFN-inducibl e factors. mRNA stimulation was followed within 24 h by induction of membra ne CD38, which coincided with rises of CD38-specific ectoenzymatic activiti es, that is, NAD(+) glycohydrolase, (A/G)DP-ribosyl cyclase, and cyclic ADP ribose hydrolase activities. IFN failed to induce or upregulate the other CD38-related ectoenzymes analyzed, that is, CD39, CD73, CD157, and PC1, Sim ilarly, treatment of leukemic cells of patients with B chronic lymphocytic leukemia (B-CLL) with IFN resulted in an increase in CD38 mRNA mirrored by plasma membrane upregulation of CD38 and NAD(+) glycohydrolase activity. Fu rther investigation in relation to CD38 gene activation and B-CLL behavior remains to be defined.