Amifostine does not preferentially stimulate the growth of residual polyclonal progenitor cells in myelodysplastic syndromes.
Amifostine is a phosphorylated aminothiol that has besides anti-oxidative and cytoprotective properties, also survival- and growth-promoting effects on hematopoietic progenitor cells. Clinical studies have demonstrated that infusions with amifostine are able to increase erythro-, myelo-, and thrombopoiesis in some patients with myelodysplastic syndromes (MDS). Since clonal and non-clonal progenitors can coexist in early phase MDS, we have studied if amifostine exerts a selective growth-promoting effect on clonal or non-clonal cells. For this purpose, purified CD34(+) marrow progenitors from nine female MDS patients were grown in short- and long-term cultures. Clonality was studied on individual colonies using polymorphisms in the human androgen receptor assay (HUMARA) locus. Three patients had growth of residual non-clonal progenitors at baseline. Continuous exposure to 100nM amifostine exerted a growth-promoting effect on progenitors in 50% of the patients. HUMARA patterns of individual colony-forming unit granulocyte macrophage (CFU-GM; 5/9) and 5 week long-term culture-initiating cells (LTC-IC; 2/9) were compared without and with amifostine exposure. We did not observe preferential stimulation of clonal or non-clonal progenitors. Based on these results, the stimulation of committed and immature progenitor growth in MDS by amifostine, is non-selective and does not favor nor suppress the growth of residual non-clonal cells.
Delforge
Michel
M
Department of Hematology, Division of Internal Medicine, University Hospital Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium.
Raets
Vicky
V
Van Duppen
Victor
V
Boogaerts
Marc
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000494:pharmacology*; D000753:Anemia, Refractory / Q000473:pathology; D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism
D018952:Antigens, CD34; D017931:DNA Primers; D011837:Radiation-Protective Agents; D011944:Receptors, Androgen; D004999:Amifostine