Abstract
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.
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Rafat Abonour, Indiana University School of Medicine, Indianapolis, IN, USA
Ray Alexanian, MD Anderson, Houston, TX, USA
Kenneth Anderson, DFCI, Boston, MA, USA
Michael Attal, Purpan Hospital, Toulouse, France
Herve Avet-Loiseau, Institute de Biologie, Nantes, France
Ashraf Badros, University of Maryland, Baltimore, MD, USA
Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
Joan Bladé, Hospital Clinica, Barcelona, Spain
Bart Barlogie, MIRT UAMS Little Rock, AR, USA
Regis Batille, Institute de Biologie, Nantes, France
Meral Beksac, Ankara University, Ankara, Turkey
Andrew Belch, Cross Cancer Institute, Alberta, Canada
Bill Bensinger, Fred Hutchinson Cancer Center, Seattle, WA, USA
Mario Boccadoro, University of Torino, Torino, Italy
Michele Cavo, Universita di Bologna, Bologna, Italy
Wen Ming Chen, MM Research Center of Beijing, Beijing, China
Tony Child, Leeds General Hospital, Leeds, UK
James Chim, Department of Medicine, Queen Mary Hospital, Hong Kong
Ray Comenzo, Tufts Medical Center, Boston, MA, USA
John Crowley, Cancer Research and Biostatistics, Seattle, WA, USA
William Dalton, H Lee Moffitt, Tampa, FL, USA
Faith Davies, Royal Marsden Hospital, London, England
Cármino de Souza, Univeridade de Campinas, Caminas, Brazil
Michel Delforge, University Hospital Gasthuisberg, Leuven, Belgium
Meletios Dimopoulos, Alexandra Hospital, Athens, Greece
Angela Dispenzieri, Mayo Clinic, Rochester, MN, USA
Brian GM Durie, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, USA
Hermann Einsele, Universitätsklinik Würzburg, Würzburg, Germany
Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France
Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos Aires, Argentina
Jean-Paul Fermand, Hopitaux de Paris, Paris, France
Rafael Fonseca, Mayo Clinic Arizona, Scottsdale, AZ, USA
Gosta Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden
Morie Gertz, Mayo Clinic, Rochester, MN, USA
John Gibson, Royal Prince Alfred Hospital, Sydney, Australia
Sergio Giralt, MD Anderson Cancer Center, Houston, TX, USA
Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany
Philip Greipp, Mayo Clinic, Rochester, MN, USA
Roman Hajek, Brno University, Brno, Czech Republic
Izhar Hardan, Tel Aviv University, Tel Aviv, Israel
Jean-Luc Harousseau, Institute de Biologie, Nantes, France
Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan
Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan
Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia
Vania Hungria, Clinica San Germano, Sao Paolo, Brazil
Shinsuke Ida, Nagoya City University Medical School, Nagoya, Japan
Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa
Sundar Jagannath, St Vincent's Comprehensive Cancer Center, New York, NY, USA
Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China
Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia
Michio Kawano, Yamaguchi University, Ube, Japan
Nicolaus Kröger, University Hospital Hamburg, Hamburg, Germany
Shaji Kumar, Department of Hematology, Mayo Clinic, MN, USA
Robert Kyle, Department of Laboratory Med. and Pathology, Mayo Clinic, MN, USA
Juan Lahuerta, Grupo Espanol di Mieloma, Hospital Universitario, Madrid, Spain
Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea
Xavier LeLeu, Hospital Huriez, CHRU Lille, France
Suzanne Lentzsch, University of Pittsburgh, Pittsburgh, PA, USA
Henk Lokhorst, University Medical CenterUtrecht, Utrecht, The Netherlands
Sagar Lonial, Emory University Medical School, Atlanta, GA, USA
Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria
Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil
Maria Mateos, University of Salamanca, Salamanca, Spain
Jayesh Mehta, Northwestern University, Chicago, IL, USA
GianPaolo Merlini, University of Pavia, Pavia, Italy
Joseph Mikhael, Mayo Clinic Arizona, Scottsdale, AZ, USA
Philippe Moreau, University Hospital, Nantes, France
Gareth Morgan, Royal Marsden Hospital, London, England
Nikhil Munshi, Diane Farber Cancer Institute, Boston, MA, USA
Ruben Niesvizky, Weill Medical College of Cornell University, New York, NY, USA
Yana Novis, Hospital SírioLibanês, Bela Vista, Brazil
Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela
Robert Orlowski, MD Anderson Cancer Center, Houston, TX, USA
Antonio Palumbo, Cathedra Ematologia, Torino, Italy
Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina
Linda Pilarski, University of Alberta, Alberta, Canada
Raymond Powles, Leukaemia & Myeloma, Wimbledon, England
S. Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA
Donna Reece, Princess Margaret Hospital, Toronto, Canada
Tony Reiman, Cross Cancer Institute, Alberta, Canada
Paul Richardson, Dana Farber Cancer Institute, Boston, MA, USA
Angelina Rodriquez Morales, Bonco Metro Politano de Sangre, Caracas, Venezuela
Orhan Sezer, Department of Hem/Onc, Universitatsklinikum Charite, Berlin, Germany
John Shaughnessy, MIRT UAMS, Little Rock, AR, USA
Kazuyuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan
David Siegel, Hackensack, Cancer Center, Hackensack, NJ, USA
Jesus San Miguel, University of Salamanca, Salamanca, Spain
Chaim Shustik, McGill University, Montreal, Canada
Seema Singhal, Northwestern University, Chicago, IL, USA
Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands
Andrew Spencer, The Alfred Hospital, Melbourne, Australia
Edward Stadtmauer, University of Pennsylvania, Philadelphia, PA, USA
A Keith Stewart, Mayo Clinic Arizona, Scottsdale, AZ, USA
Patrizia Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy
Guido Tricot, Huntsman Cancer Institute, Salt Lake City, UT, USA
Ingemar Turesson, Department of Hematology, Malmo University, Malmo, Sweden
Brian Van Ness, University of Minnesota, Minneapolis, MN, USA
Ivan Van Riet, Brussels Vrija University, Brussels, Belgium
Robert Vescio, Cedars-Sinai Cancer Center, Los Angeles, CA, USA
David Vesole, Loyola University Chicago, IL, USA
Anders Waage, University Hospital, Trondheim, Norway NSMG
Michael Wang, MD Anderson, Houston, TX, USA
Donna Weber, MD Anderson, Houston, TX, USA
Jan Westin, Sahlgrenska University Hospital, Gothenburg, Sweden
Keith Wheatley, University of Birmingham, Birmingham, UK
Dina B Yehuda, Department of Hematology, Hadassah University Hospital, Hadassah, Israel
Jeffrey Zonder, SWOG, Department of Hem/Onc., Karmanos Cancer Institute, MI, USA
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Fonseca, R., Bergsagel, P., Drach, J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 23, 2210–2221 (2009). https://doi.org/10.1038/leu.2009.174
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DOI: https://doi.org/10.1038/leu.2009.174
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