Persistent decrease in proliferative potential of marrow CD34(+)cells exposed to early-acting growth factors after autologous bone marrow transplantation.
Post-graft hematopoiesis is characterized by long-term quantitative deficiency in marrow progenitor cells in both autologous and allogenic settings. In order to evaluate the function of post-graft progenitor cells, the proliferative capacity of marrow CD34(+) cells was evaluated in 10 patients 6 months after autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma and compared to that of 10 patients before ABMT and 10 normal controls. Immuno-selected CD34(+) cells were cultured for 7 days in liquid serum-free medium with a combination of early-acting GF consisting of stem cell factor, IL-3 and IL-1beta. Clonogenic efficiency of unselected cells for CFU-GM and BFU-E was decreased in post-graft patients compared to pre-graft and control patients. However, clonogenic efficiency of selected CD34(+) cells for CFU-GM was not different in post-graft, pre-graft and control patients but BFU-E values of post-graft patients remained lower than those of control patients. Decreased percentages of CD34(+) CD38(-) cells were observed in both post-graft and pre-graft patients while those of CD34(+) c-kit(+) cells were similar in all three patient groups. After 7-day liquid culture, expansion yields of total progenitor cells were significantly lower in post-graft patients (147 +/- 28%) than in pre-graft (255 +/- 27%) and control patients (246 +/- 23%). Post-graft deficiency in progenitor cell expansion was particularly marked for BFU-E (61 +/- 24%) compared to pre-graft patients (220 +/- 82%) and to controls (349 +/- 82%). These results indicate impaired proliferative potential of marrow CD34(+) cells several months after ABMT involving erythroid progenitor cells and/or commitment towards erythroid lineage from a more immature stage (pre-CFU).
Domenech
J
J
UPRES-EA 3249, Laboratory of Hematology, University Hospital of Tours, Tours, France.
Cartron
G
G
Clement
N
N
Estienne
M-H
MH
Herault
O
O
Truglio
D
D
Benboubker
L
L
Roingeard
F
F
Desbois
I
I
Colombat
P
P
Binet
C
C
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016895:Culture Media, Serum-Free; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019089:Stem Cell Factor / Q000494:pharmacology*; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D007375:Interleukin-1; D007377:Interleukin-3; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit