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Increased expression of macrophage inflammatory protein-1α on trephine biopsies correlates with extensive bone disease, increased angiogenesis and advanced stage in newly diagnosed patients with multiple myeloma

Leukemia volume 23, pages 2177–2181 (2009)Cite this article

The biology of bone destruction in multiple myeloma (MM) includes an increased activity of osteoclasts, which is accompanied by a reduction in osteoblast function leading to a high resorptive phase and subsequent bone loss. Macrophage inflammatory protein-1α (MIP-1α) is a low-molecular-weight chemokine that belongs to the regulated upon activation, normal T-cell-expressed and presumably secreted (RANTES) family. MIP-1α is produced by myeloma cells and enhances osteoclast activity in the myeloma microenvironment, acting on differentiated osteoclasts in a dose-dependent manner.1 Earlier studies have shown that MIP-1α levels are elevated in the bone marrow plasma and the serum of patients with MM, whereas serum MIP-1α and the gene expression of MIP-1α correlate with the presence of lytic lesions in MM.2, 3 MIP-1α is a chemoattractant for monocytes and recently it was shown that monocytes may give rise to vascular endothelium.4 Thus, our hypothesis was that myeloma cells express MIP-1α and other chemoattractants for monocytes and macrophages, and this expression correlated with both increased bone resorption (as osteoclasts are originated from a macrophage lineage precursor cell) and increased angiogenesis. The aim of our study was to evaluate the role of MIP-1α immunoexpression on trephine biopsies in the development of myeloma bone disease and examine possible correlations between MIP-1α expression and clinical data, including prognostic factors of MM and angiogenesis.

Patients with newly diagnosed MM having a bone marrow trephine biopsy before any kind of anti-myeloma therapy administration, including bisphosphonates and steroids, were eligible for participating in the study. Evidence of bone involvement at the time of diagnosis was documented using plain radiography. A grading of bone morbidity into three groups according to the radiographic evaluation of the skeleton was made. Group A included patients with no lytic lesions, group B included patients with osteolytic lesions in 1–3 areas and group C included patients with lytic lesions in more than three areas and/or a pathological fracture due to MM. The study was conducted after obtaining an approval from the Ethics Committee/Institutional Review Board and an informed consent was obtained from all patients before any intervention.

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Authors and Affiliations

  1. Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra University Hospital, Athens, Greece

    M Roussou, M A Dimopoulos, E Kastritis, M Migkou, D Christoulas, M Gavriatopoulou, F Zagouri, C Matsouka & E Terpos

  2. Department of Hemopathology, Evangelismos General Hospital, Athens, Greece

    A Tasidou & D Anagnostou

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  1. M Roussou
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Correspondence to E Terpos.

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Roussou, M., Tasidou, A., Dimopoulos, M. et al. Increased expression of macrophage inflammatory protein-1α on trephine biopsies correlates with extensive bone disease, increased angiogenesis and advanced stage in newly diagnosed patients with multiple myeloma. Leukemia 23, 2177–2181 (2009). https://doi.org/10.1038/leu.2009.130

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