All‐trans‐retinoic acid up‐regulates CD38 but not c‐Kit antigens on human marrow CD34+ cells without recruitment into cell cycle

Retinoids, especially all‐trans‐retinoic acid (ATRA), are well known for their differentiating activity on HL‐60 cells. Moreover ATRA induces CD38 antigen overexpression on these cells. In this study we examined the effects of ATRA on purified normal CD34+ cells from adult human marrows incubated with ATRA (1 μM) or stem cell factor (SCF) after 7 d liquid cultures in serum‐deprived medium. Before and after the incubation, CD34+ cells were studied by flow cytometry to evaluate the cell‐surface expression of CD38 and c‐Kit antigens and the cycle status of these cells using high‐resolution analysis (DNA content v Ki‐67 antigen expression) to clarify the functional meaning of antigenic variations. When compared with control cultures, ATRA‐treated cells displayed changes in their immunophenotypic profile. Particularly relevant was the up‐regulation of CD38 antigen with a mean (±SEM) fold increase of 2.1 ± 0.1 (P = 0.028) for geometric mean fluorescence intensity (GMFI), without modulation of c‐Kit expression. SCF only down‐regulated expression of c‐Kit with a fold decrease of 4.6 ± 0.9 for GMFI (P = 0.043). Unlike SCF, ATRA did not induce CD34+ cells to entry into cell cycle despite increased levels of surface CD38 antigen. Moreover morphological and functional assays did not argue for an ATRA‐induced maturation process. Contrary to steady‐state cells, CD34+ cells treated with pharmacological doses of ATRA alone displayed CD38 over‐expression without change in c‐Kit levels and cycle status, suggesting an absence of maturation pressure.