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The effects of interferon‐α on the proliferation of CML progenitor cells in vitro are not related to the precise position of the M‐BCR breakpoint
Author(s) -
Dowding C.,
Guo AP.,
Maisin D.,
Gordon M. Y.,
Goldman J. M.
Publication year - 1991
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1991.tb07972.x
Subject(s) - progenitor cell , clonogenic assay , philadelphia chromosome , bone marrow , myeloid , interferon , breakpoint cluster region , immunology , cancer research , biology , stromal cell , microbiology and biotechnology , stem cell , in vitro , chromosomal translocation , genetics , receptor , gene
Summary We investigated the effects of brief (2 h) and continuous exposure to recombinant interferon‐α 2a (rIFN‐α) 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‐α 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‐α. Erythroid colony formation by normal, but not by CML BFU‐E, was inhibited by relatively low concentrations (100 U/ml) of rIFN‐α. 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‐α. We found no difference in the sensitivity to rIFN‐α 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‐α 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‐α is independent of the type of BCR/ABL message present in the cells. The clinical efficacy of rIFN‐α 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.