Interferon-alpha alters the distribution of CFU-GM between the adherent and nonadherent compartments in long-term cultures of chronic myeloid leukemia marrow.
We studied the effect of recombinant interferon-alpha 2a (IFN alpha) on the interaction between stromal cells and granulocyte-macrophage colony-forming units (CFU-GM) from the marrow of normal individuals and chronic myeloid leukemia (CML) patients in chronic phase in long-term bone marrow cultures using preformed stromal layers. These stromal layers were established with marrow cells from normal allogeneic donors and grown to confluence in the presence or absence of IFN alpha at low concentration (100 U/ml). The number of CML CFU-GM localized within IFN alpha-treated stromal layers was significantly greater than the corresponding number localized within control stromal layers. Conversely, the distribution of normal CFU-GM between the adherent and nonadherent compartments was unaffected by IFN alpha treatment of the stromal layer. Preincubation of CML marrow cells with IFN alpha did not alter this distribution, so the observed effect of IFN alpha must be due to a primary action on stromal layers. Thus, in addition to its well known antiproliferative effect, IFN alpha enhances the capacity of marrow stromal cells to bind and/or retain CML progenitor cells, and the resulting restoration of normal regulatory control may be the basis for the selectivity of IFN alpha in CML.
Osterholz
J
J
MRC/LRF Leukaemia Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Dowding
C
C
Guo
A P
AP
Siczkowski
M
M
Goldman
J M
JM
D001853:Bone Marrow / Q000473:pathology* / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D006098:Granulocytes / Q000473:pathology* / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011994:Recombinant Proteins