ALL-TRANS-RETINOIC ACID UP-REGULATES CD38 BUT NOT C-KIT ANTIGENS ON HUMAN MARROW CD34(-CYCLE() CELLS WITHOUT RECRUITMENT INTO CELL)

Retinoids, especially all-trans-retinoic acid (ATRA), are well known f or their differentiating activity on HL-60 cells, Moreover ATRA induce s CD38 antigen over-expression on these cells, In this study we examin ed the effects of ATRA on purified normal CD34(+) cells from adult hum an marrows incubated with ATRA (1 mu M) or stem cell factor (SCF) afte r 7d liquid cultures in serum-deprived medium. Before and after the in cubation, CD34+ cells were studied by flow cytometry to evaluate the c ell-surface expression of CD38 and c-Kit antigens and the cycle status of these cells using high-resolution analysis (DNA content v Ki-67 an tigen expression) to clarify the functional meaning of antigenic varia tions. When compared with control cultures. ATRA-treated cells display ed changes in their immunophenotypic profile, Particularly relevant wa s the up-regulation of CD38 antigen with a mean (+/- SEM) fold increas e of 2.1 +/- 0.1 (P = 0.028) for geometric mean fluorescence intensity (GMFI), without modulation of c-Kit expression. SCF only down-regulat ed 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 treate d with pharmacological doses of ATRA alone displayed CD38 over-express ion without change in c-Kit levels and cycle status, suggesting an abs ence of maturation pressure.