International Myeloma Working Group molecular classification of multiple myeloma: spotlight review

• Published in: Leukemia Vol. 23; no. 12; pp. 2210 - 2221
• Main Authors: Fonseca, R, Bergsagel, P L, Drach, J, Shaughnessy, J, Gutierrez, N, Stewart, A K, Morgan, G, Van Ness, B, Chesi, M, Minvielle, S, Neri, A, Barlogie, B, Kuehl, W M, Liebisch, P, Davies, F, Chen-Kiang, S, Durie, B G M, Carrasco, R, Sezer, Orhan, Reiman, Tony, Pilarski, Linda, Avet-Loiseau, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2009; Nature Publishing Group
• Subjects: Abnormalities; Biological and medical sciences; Cancer; Cancer Research; Care and treatment; Cell proliferation; Cell survival; Chromosome 1; Chromosome deletion; Chromosome translocations; Chromosomes; Classification; Clinical trials; Critical Care Medicine; Cytogenetic Analysis; Cytogenetics; Deregulation; Diagnosis; Evolution; Gene expression; Gene Expression Profiling; Genetic screening; Genetic testing; Genetic Testing - methods; Genetics; Heavy chains; Hematologic and hematopoietic diseases; Hematology; Hospitals; Humans; Hybridization; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunoglobulins; Immunopathology; Intensive; Internal Medicine; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical prognosis; Medical research; Medical sciences; Medicine; Medicine & Public Health; Multiple myeloma; Multiple Myeloma - classification; Multiple Myeloma - genetics; Mutation; Nosology; Oncology; Plasma cells; Prognosis; spotlight-review; Survival; Working groups; Canada; United States; United States > US; multiple myeloma; molecular; genetics; cytogenetics; gene expression profiling; prognosis; Immunopathology; Prognosis; Hematology; B cell neoplasm; Malignant hemopathy; Review; Lymphoid neoplasm; Myeloma; Gene expression profile; Immunoglobulinopathy; Lymphoproliferative syndrome; Classification; Cytogenetics; Genetics; Bibliographic review; Cancer; International
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.174

Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinicopathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of chromosomes 13 and 17 and abnormalities of chromosome 1 (1p deletion and 1q amplification). Other key drivers of cell survival and proliferation have also been identified such as nuclear factor- B-activating mutations and other deregulation factors for the cyclin-dependent pathways regulators. Further understanding of the biological subtypes of the disease has come from the application of novel techniques such as gene expression profiling and array-based comparative genomic hybridization. The combination of data arising from these studies and that previously elucidated through other mechanisms allows for most myeloma cases to be classified under one of several genetic subtypes. This paper proposes a framework for the classification of myeloma subtypes and provides recommendations for genetic testing. This group proposes that genetic testing needs to be incorporated into daily clinical practice and also as an essential component of all ongoing and future clinical trials.