The Effects of Interferon-alpha On the Proliferation of Cml Progenitor Cells-invitro Are Not Related To the Precise Position of the M-bcr Breakpoint

Dowding, C.;Guo, AP.;Maisin, D.;Gordon, MY.;Goldman, JM.
(1991) British Journal of Haematology — Vol. 77, n° 2, p. 165-171 (1991)

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  • Dowding, C.
    Author
  • Guo, AP.
    Author
  • Maisin, D.
    Author
  • Gordon, MY.
    Author
  • Goldman, JM.
    Author
Abstract
We investigated the effects of brief (2 h) and continuous exposure to recombinant interferon-alpha2a (rIFN-alpha) on the proliferation of primitive (blast colony-forming cells, Bl-CFC) and committed myeloid progenitor cells (BFU-E and GM-CFC) derived from blood and bone marrow of patients with chronic myeloid leukaemia (CML) and normal subjects. In all three clonogenic assays, rIFN-alpha suppressed colony formation in a dose-dependent manner. No differences were detected in the proliferation of CML or normal Bl-CFC and GM-CFC exposed to rIFN-alpha. Erythroid colony formation by normal, but not by CML BFU-E, was inhibited by relatively low concentrations (100 U/ml) of rIFN-alpha. However, in patients whose blood or marrow contained a mixture of Philadelphia chromosome (Ph)-positive and Ph-negative BFU-E, cytogenetic analysis of individual erythroid colonies showed no differential inhibition by rIFN-alpha. We found no difference in the sensitivity to rIFN-alpha of GM-CFC from patients whose leukaemic cells expressed BCR/ABL mRNA with the b2a2 junction and that of GM-CFC from patients with the b3a2 mRNA. We conclude that (1) rIFN-alpha does not have a significant leukaemia-specific effect on the progenitor cells detected in these assays, and (2) the sensitivity of CML GM-CFC to rIFN-alpha is independent of the type of BCR/ABL message present in the cells. The clinical efficacy of rIFN-alpha could be due to selective toxicity to cells not assayed in this study, to effects on accessory cells or to alterations induced in progenitor cell/stromal cell interactions.
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Dowding, C., Guo, AP., Maisin, D., Gordon, MY., & Goldman, JM. (1991). The Effects of Interferon-alpha On the Proliferation of Cml Progenitor Cells-invitro Are Not Related To the Precise Position of the M-bcr Breakpoint. British Journal of Haematology, 77(2), 165-171. https://doi.org/10.1111/j.1365-2141.1991.tb07972.x (Original work published 1991)