CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T-and B-lymphocytes. In myeloid cells, CD38 is expressed during early stages of differentiation. Virtually no information is available on regulation and functions of CD38. Recently we reported that all-trans-retinoic acid (ATRA) is a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells. Here we report that ATRA-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid-α receptor (RARα). ATRA failed to induce CD38 expression in a mutant subclone of the HL-60 myeloid leukemia cell line (designated HL-60R) that is relatively resistant to ATRA-induced granulocytic differentiation. Retroviral vector-mediated transduction of RA receptor (RARα) into this HL-60R subclone completely restored the sensitivity of these cells to ATRA in terms of their ability to express CD38. In contrast, CD38 expression was not inducible by ATRA in HL-60R cells, transfected with a functional RARβ, RARγ, or RXRα receptor. Induction of CD38 in acute promyelocytic and acute myeloblastic leukemia cells was independent of ATRA-induced cytodifferentiation. Following culture with ATRA, increased CD38 protein levels were also observed in normal CD34+ bone marrow cells, but not on normal circulating granulocytes. From these results, we conclude that CD38 is ATRA inducible in myeloid leukemia cells and normal CD34+ bone marrow cells. This effect is independent of differentiation and is mediated by RARα in HL-60 cells, suggesting a similar role for RARα in CD38 expression in other hematopoietic cells.


This work was supported in part by Argus Pharmaceuticals, Inc., The Woodlands, TX, and by grants from the Food and Drug Administration (FD-R-000923), from NIH (CA 55397, CA 57369, CA 16672, and CA 55164), European Economic Community Biotechnology Project (Brussels, Belgium, BI02/CT92/0269), and Target Project “Applicazioni Cliniche Ricerca Oncologica” (Consiglio Nazionale Ricerche, Rome, Italy). K. A. R. is a special fellow of the Leukemia Society of America.

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