Progenitor cells in the blood and marrow of patients with chronic phase chronic myeloid leukaemia respond differently to macrophage inflammatory protein-1 alpha.
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a negative regulator of normal haemopoietic stem cell proliferation. Insensitivity to MIP-1 alpha of progenitor cells in chronic myeloid leukaemia (CML) could, therefore, explain myeloid expansion in this disease. We compared the effects of MIP-1 alpha on progenitor cells in normal marrow and in the blood and marrow of patients with chronic phase CML. Plastic-adherent precursors of granulocyte-macrophage colony-forming cells (P delta progenitors) are very primitive progenitor cells and are detected by incubating them for 1 week in liquid culture and assaying the CFU-GM released into the supernatant. Direct CFU-GM assays were also used in this study. Daily addition of 300 ng/ml/day of MIP-1 alpha to P delta progenitor assays of normal marrow cells suppressed CFU-GM production by 50% and in CML bone marrow P delta cultures by 20-30%. The response of CML blood P delta progenitors was heterogeneous. In five of nine cases, CFU-GM production was doubled in the presence of MIP-1 alpha and in four of nine cases, it was reduced. Addition of 100-500 ng MIP-1 alpha to direct assays of CFU-GM stimulated colony formation by normal marrow and CML blood cells to a similar extent.
Nirsimloo
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Leukaemia Research Fund Centre, Institute of Cancer Research, London, U.K.
Gordon
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MY
D001854:Bone Marrow Cells; D002478:Cells, Cultured; D054407:Chemokine CCL4; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000503:physiopathology*; D019402:Macrophage Inflammatory Proteins; D009000:Monocytes / Q000166:cytology; D015846:Monokines / Q000494:pharmacology*
D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines