Significance of macrophage inflammatory protein-1 alpha (MIP-1alpha) in multiple myeloma

Leuk Lymphoma. 2005 Dec;46(12):1699-707. doi: 10.1080/10428190500175049.


Macrophage inflammatory protein-1 alpha (MIP-1alpha) is a member of the CC chemokine family and is primarily associated with cell adhesion and migration. It is produced by myeloma (MM) cells and directly stimulates osteoclast formation and differentiation in a dose dependent way. MIP-1alpha protein levels were elevated in the bone marrow plasma of MM patients and correlated with disease stage and activity. MIP-1alpha was also elevated in the serum of myeloma patients with severe bone disease and correlated positively with bone resorption markers providing evidence for a causal role of MIP-1alpha in the development of lytic bone lesions in MM. MIP-1alpha has also been found to stimulate proliferation, migration and survival of plasma cells. Mice, which were inoculated with myeloma cells and treated with a monoclonal rat anti-mouse MIP-1alpha antibody, showed a reduction of both paraprotein and lytic lesions. In addition, MIP-1alpha enhanced adhesive interactions between myeloma and marrow stromal cells, increasing the expression of RANKL and IL-6, which further increased bone destruction and tumor burden. Myeloma patients with high MIP-1alpha serum levels have poor prognosis. The positive correlation between MIP-1alpha and beta(2)-microglobulin that has been observed in MM patients at diagnosis further supports the notion that MIP-1alpha is not only a chemokine with osteoclast activity function but is also implicated in myeloma growth and survival. Therefore, MIP-1alpha pathway may serve as a target for the development of novel anti-myeloma therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Diseases / genetics
  • Bone Diseases / pathology
  • Carrier Proteins / analysis
  • Chemokine CCL3
  • Chemokine CCL4
  • Humans
  • Macrophage Inflammatory Proteins / blood
  • Macrophage Inflammatory Proteins / genetics*
  • Membrane Glycoproteins / analysis
  • Mice
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Osteoclasts / pathology
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Survival Analysis


  • Carrier Proteins
  • Chemokine CCL3
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse