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 microM) 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 21 +/- 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.
Herault
O
O
JE 1993, Faculty of Medicine, Tours, France.
Domenech
J
J
Degenne
M
M
Bremond
J L
JL
Sensebe
L
L
Bernard
M C
MC
Binet
C
C
Colombat
P
P
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D019089:Stem Cell Factor; D014212:Tretinoin; D019009:Proto-Oncogene Proteins c-kit; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1