User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

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

Primary tabs

Dowding, C. Guo, AP. Maisin, D. Gordon, MY. Goldman, JM.

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.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 1991
Language Anglais
Journal information "British Journal of Haematology" - Vol. 77, no. 2, p. 165-171 (1991)
Peer reviewed yes
Publisher Blackwell Science Ltd (Oxford)
issn 0007-1048
e-issn 1365-2141
Publication status Publié
Affiliation UCL
Links
  1. Amenomori T., International Journal of Cell Cloning, 3, 133 (1985)
  2. Balkwill Frances R., Oliver R. T. D., Growth inhibitory effects of interferon on normal and malignant human haemopoietic cells, 10.1002/ijc.2910200405
  3. Broxmeyer H., Journal of Immunology, 131, 1300 (1983)
  4. Chomczynski Piotr, Sacchi Nicoletta, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction, 10.1016/0003-2697(87)90021-2
  5. Dowding C., Experimental Hematology, 15, 32 (1987)
  6. Dowding C., British Journal of Haematology, 74 (1990)
  7. Estrov Z., Experimental Hematology, 15, 127 (1987)
  8. Fogh J., National Cancer Institute Monographs, 49, 5 (1978)
  9. Galvani D., British Journal of Haematology, 73, 475 (1989)
  10. Gordon M. Y., Dowding C. R., Riley G. P., Goldman J. M., Greaves M. F., Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia, 10.1038/328342a0
  11. Gordon M., British Journal of Haematology, 60, 129 (1985)
  12. Greenberg P., Cancer Research, 37, 1794 (1977)
  13. Hughes Timothy, Janssen J.W.G, Morgan Gareth, Martiat Philippe, Saglio Guiseppe, Pignon J.M, Pignatti FrancoPier, Mills Ken, Keating Armand, Gluckman Eliane, Bartram C.R, Goldman J.M, False-positive results with PCR to detect leukaemia-specific transcript, 10.1016/0140-6736(90)91102-g
  14. Lee M., Blood, 74 (1989)
  15. Lee M., Blood, 73, 2165 (1989)
  16. Martiat P., Leukemia, 3, 563 (1989)
  17. McGlave P., Experimental Hematology, 15, 331 (1987)
  18. Morgan G.J., British Journal of Haematology, 76, 33 (1990)
  19. Neumann H., Experimental Hematology, 10, 587 (1982)
  20. Olidapu-Williams C., Oncology, 38, 356 (1981)
  21. Opalka B., Blood, 74, 1397 (1989)
  22. J. Sambrook, E. Fritsch, T. Maniatis, and C. Nolan (1989 ) In: Molecular Cloning (), pp.9 . 9 -9 . 9 . Cold Spring Harbor Laboratory Press.
  23. Schaefer-Rego K., Blood, 70, 448 (1987)
  24. Talpaz M., British Journal of Haematology, 64, 87 (1986)
  25. Talpaz M., New England Journal of Medicine, 314, 1065 (1986)
  26. Visani G., Russo D., Damiani D., Rizzi S., Motta M. R., Lemoli R. M., Poluzzi C., Fanin R., Zuffa E., Tosi P., Baccarani M., Tura S., Sensitivity of Ph1+ CFU-GM to human recombinant interferon ? and ? alone and in combination, 10.1007/bf00320633
Bibliographic reference Dowding, C. ; Guo, AP. ; Maisin, D. ; Gordon, MY. ; Goldman, JM.. 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. In: British Journal of Haematology, Vol. 77, no. 2, p. 165-171 (1991)
Permanent URL http://hdl.handle.net/2078.1/51244