Combined effect of interferon-gamma and tumor necrosis factor-alpha causing suppression of leukemic blast progenitors in acute myeloblastic leukemia.
The effects of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) on the growth of leukemic blast progenitors in 6 acute myeloblastic leukemia (AML) patients, 1 chronic myelocytic leukemia (CML) patient in blast crisis and a granulocyte colony-stimulating factor-(G-CSF-) dependent OCI/AML1a cell line established from an AML patient, were studied. Cells of fresh blood samples and the OCI-AML1a cell line were cultured in methylcellulose media and suspension culture in the presence of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) supplemented as a growth stimulatory factor. Both cytokines suppressed the primary and secondary colony formation in methylcellulose culture of leukemic blast progenitors. The recovery of clonogenic cells in suspension culture was also suppressed by IFN-gamma and TNF-alpha. The primary colony formation in methylcellulose reflects the terminal divisions of leukemic blast progenitors, while the secondary colony formation in methylcellulose and the clonogenic cell recovery in suspension have been considered to reflect their self-renewal capacity. Therefore, IFN-gamma and TNF-alpha are considered to be effective in suppressing not only the terminal divisions but also self-renewal of leukemic blast progenitors. When both cytokines were added simultaneously to cultures, the suppressive effect of each cytokine was enhanced. The results may suggest the effectiveness of IFN-gamma and TNF-alpha in the treatment of leukemia.
Nara
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Laboratory Medicine, Tokyo Medical and Dental University, Japan.
D001752:Blast Crisis / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
D007155:Immunologic Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor