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Multiple myeloma is a malignant monoclonal plasma cell disorder that is characterized by end-organ damage such as anemia, renal insufficiency, hypocalcemia and bone lesions. Multiple myeloma is a genetically complex disease that is becoming more common in today’s ageing population. Myeloma belongs to a group of related paraproteinaemias that are characterized by an abnormal clonal plasma cell infiltration in the bone marrow. Various distinct clinical phases of myeloma can be recognized, including monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM; also known as asymptomatic myeloma).
The basic premise underlying the initiation and progression of myeloma is that multiple mutations in different pathways deregulate the intrinsic biology of the plasma cell, changing it in ways that generate the features of myeloma. Many of the genes and pathways mediating this transformation process have now been characterized. At the cytogenetic level, the myeloma genome is recognized as being complex and more reminiscent of epithelial cancers than of more simple leukemia. Many of the genetic lesions that lead to myeloma have been defined. They can be categorized as inherited variation, translocations, mutations, copy number abnormalities, and methylation and microRNA (miRNA) abnormalities. The net biological impact of such events is to modify the behavior of the MPC, leading to the key hallmarks of myeloma. In addition to the genetic changes, intraclonal heterogeneity of myeloma-propagating cells (MPCs) is emerging as a further level of complexity. In addition, a range of signaling pathways are deregulated in myeloma and contribute towards pathogenesis through associations with survival, proliferation, apoptosis, migration, and drug resistance. Other cellular processes such as DNA repair, RNA editing, cell differentiation and protein homeostasis may also contribute towards myeloma genesis by aberrant functioning.
Myeloma serves as a paradigm for the development of new drugs by targeting the tumor in its microenvironment, since bench-to-bedside translation of novel agents has led to multiple novel therapies and the doubling of patient survival over the past decade. Several classes of agents including next-generation proteasome inhibitors, selective histone-deacetylase inhibitors, immunomodulatory agents, antibody and antitumor immunotherapy approaches are currently undergoing preclinical and clinical evaluation. Strategies for the future include the development of next-generation agents using the platform of existing agents, development of novel agents that target pathways involved in the pathogenesis of myeloma, therapies aimed at accessory cells and cytokines, and immune-based therapies. Targeting validated antigens in patients who are genetically defined as the ones who are most likely to respond can similarly accelerate evolution of immune-based therapies.
Creative Biogene, as a leading biotechnology company, is able to offer various multiple myeloma pathway related products including stable cell lines, viral particles and clones for your pathogenesis study and drug discovery projects.