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 over-expression 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 mu M) or stem cell factor (SCF) after 7d 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 SCE 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.