The role of interleukin-6 and interleukin-6/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma.
Multiple myeloma (MM) is a plasma-cell disorder in which malignant plasma cells accumulate in the bone marrow and usually produce a monoclonal immunoglobulin. Usual presenting features of overt MM include recurrent osteolytic lesions, bacterial infections, anemia and renal insufficiency. MM is responsible for about 1 percent of all cancer-related deaths in Western countries. Its epidemiologic pattern remains obscure, and its cause unknown [1]. The presence of somatic mutations within the immunoglobulin genes of myeloma cells indicate that the putative myeloma-cell precursors have been stimulated by antigens within germinal centers and are either memory B cells or migrating plasmablasts. Myeloma cells proliferate slowly in the bone marrow and display a weak apoptotic index in vivo [2]. This suggest that some defects in the apoptotic process could be involved in this neoplasia. Interleukin-6 (IL-6) is known to be an essential survival factor of myeloma cells and to protect them from apoptosis induced by different stimuli (e.g. dexamethasone, CD95, serum starvation, gamma-irradiation). More recently, important works have been devoted to the biology of the soluble form of the IL-6R alpha i.e., sIL-6R alpha. These works give IL-6/sIL-6R alpha complex an important role in the biology of IL-6. The purpose of the current review is to emphasize the role of this complex in the pathogenesis of MM.
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INSERM U. 463, Institut de Biologie, 9, quai Moncousu, 44035 Nantes Cedex 01, France.
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Amiot
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D000818:Animals; D001853:Bone Marrow / Q000098:blood supply; D001854:Bone Marrow Cells / Q000276:immunology; D001862:Bone Resorption; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D009101:Multiple Myeloma / Q000209:etiology* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010006:Osteoblasts / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D046911:Macromolecular Substances; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C113250:interleukin-6 receptor alpha