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

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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Correspondence to R Fonseca.

Additional information

Members of the IMWG are listed in the appendix.

Appendix

Appendix

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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Keywords

  • multiple myeloma
  • genetics
  • cytogenetics
  • molecular
  • prognosis
  • gene expression profiling

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