The growth inhibitory role and potential clinical value of macrophage inflammatory protein 1 alpha in myeloid leukaemias.
The control of primitive haemopoietic progenitor cell proliferation in vitro can be achieved with combinations of growth stimulatory cytokines. Acting in apparent opposition to these growth stimulators are growth inhibitory substances, including prostaglandins, cytokines and chemokines which bind to specific cognate cell surface receptors and promote signal transduction events that interfere with cellular proliferation. Within the bone marrow microenvironment, significant quantities of both growth inhibitors and growth promoters can be detected. The ratio of their concentrations within microenvironmental niches of the marrow may regulate primitive blood cell production. The potential exists, therefore, for the disregulation of haemopoiesis via the disruption of the balance between positive and negative regulators of haemopoietic progenitor proliferation. In one particular disease, chronic myeloid leukaemia (CML), there is a lack of response of leukaemic cells to the chemokine growth inhibitor, Macrophage Inflammatory Protein-1alpha (MIP-1alpha). The role of MIP-1alpha in regulation of haemopoiesis, the response of CML progenitor cells and other myeloid leukaemic cells to this chemokine, and the reasons for lack of response to MIP-1alpha in leukaemic cells are reviewed.
Leukaemia Research Fund Cellular Development Unit, Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, UK.
P J
PJ
Owen-Lynch
L G
LG
Czaplewski
M G
MG
Hunter
A D
AD
Whetton
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D019402:Macrophage Inflammatory Proteins / Q000627:therapeutic use*; D019707:Receptors, Chemokine / Q000187:drug effects*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; C080633:macrophage inflammatory protein 1alpha receptor