The effect of tetraethylenepentamine, a synthetic copper chelating polyamine, on expression of CD34 and CD38 antigens on normal and leukemic hematopoietic cells.
We have previously found that the synthetic polyamine tetraethylenepentamine (TEPA) significantly delayed differentiation and prolonged expansion of cord-blood derived HPC in cytokine-supplemented cultures. Most HPC have the CD34+CD38+ phenotype, but the minority CD34+38- cells are primitive subset of HPC that have the potential for long-term repopulation in vivo. We investigated the effect of TEPA on the CD34/CD38 surface antigen expression of human myeloid leukemia cell lines as well as normal cord blood derived hematopoietic cells. Confirming previous results, our data showed that both the leukemic and normal cells increased their CD38 expression when grown in serum-containing medium or when treated with retinoic acid. In the present study, we found that TEPA inhibited CD38 under these conditions in both normal and leukemic cells. As for CD34, TEPA increased the proportion of CD34 cells in short- and long-term normal cultures but not in the leukemic cell lines. These results suggest that ex vivo expansion of HPC depends on the presence of CD34+CD38- cells and that TEPA prolongs HPC expansion by inhibiting the CD38- to CD38+ transition.
Prus
Eugenia
E
Department of Haematology, Hadassah University Hospital, Israel.
Peled
Tony
T
Fibach
Eitan
E
D036541:ADP-ribosyl Cyclase / Q000032:analysis*; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000172:deficiency; D005029:Ethylenediamines / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008562:Membrane Glycoproteins; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology; D011073:Polyamines / Q000494:pharmacology
D015703:Antigens, CD; D018952:Antigens, CD34; D002614:Chelating Agents; D005029:Ethylenediamines; D008562:Membrane Glycoproteins; D011073:Polyamines; D003300:Copper; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C034269:tetraethylenepentamine