The comparison of 2-chlorodeoxyadenosine (2-Cd A) in combination with interferon alpha (IFN alpha) or interferon gamma (IFN gamma) on granulocyte-macrophage progenitor cells (CFU-GM) and clonogenic blasts in (CFU-L) in vitro cultures.
In the present in vitro study we investigated the influence of 2-chlorodeoxyadenosine (2-CdA) and interferon gamma (IFNgamma) on the clonal growth of granulocyte macrophage progenitor (CFU-GM) cells from 10 normal individuals and from 10 patients with chronic myeloid leukemia (CML) and on CFU-L blasts from 10 patients with acute myeloid leukemia (AML). 2-CdA was added to the culture medium at 20nM/l, 40nM/l and 80nM/l concentrations and IFNgamma at concentrations of 10(2)U/ml, 10(3)U/ml and 10(4)U/ml. Both agents were used alone and in combination with these different concentrations. We observed a decrease in the number of colonies formed by CML CFU-GM as well as by AML CFU-L in a dose-dependent manner. The drugs used alone inhibited to a higher degree the growth of CML than of normal CFU-GM progenitors. 2-CdA and IFN gamma showed the greatest additive effect on the growth of CFU-L blasts at the concentrations of 80nM/l and 10(4)U/ml, respectively. We compared our results with previous in vitro studies in which we have demonstrated the synergistic inhibitory effect of 2-CdA and IFN alpha on both normal and leukemic hematopoiesis. We suggest that the greatest inhibitory effect is observed when 2-CdA and IFN alpha at the highest concentration are added together to the culture of AML CFU-L blasts.
2nd Department of Internal Medicine, Medical University of Lodz, Poland.
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Korycka
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D017338:Cladribine / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011994:Recombinant Proteins
D016898:Interferon-alpha; D011994:Recombinant Proteins; D017338:Cladribine; D007371:Interferon-gamma