Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Multiple Myeloma, Gammopathies

Gene signature combinations improve prognostic stratification of multiple myeloma patients

Leukemia volume 30, pages 1071–1078 (2016)Cite this article

Subjects

Abstract

Multiple myeloma (MM) is a plasma cell neoplasm with significant molecular heterogeneity. Gene expression profiling (GEP) has contributed significantly to our understanding of the underlying biology and has led to several prognostic gene signatures. However, the best way to apply these GEP signatures in clinical practice is unclear. In this study, we investigated the integration of proven prognostic signatures for improved patient risk stratification. Three publicly available MM GEP data sets that encompass newly diagnosed as well as relapsed patients were analyzed using standardized estimation of nine prognostic MM signature indices and simulations of signature index combinations. Cox regression analysis was used to assess the performance of simulated combination indices. Taking the average of multiple GEP signature indices was a simple but highly effective way of integrating multiple GEP signatures. Furthermore, although adding more signatures in general improved performance substantially, we identified a core signature combination, EMC92+HZDCD, as the top-performing prognostic signature combination across all data sets. In this study, we provided a rationale for gene signature integration and a practical strategy to choose an optimal risk score estimation in the presence of multiple prognostic signatures.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Bergsagel PL, Kuehl WM . Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 2005; 23: 6333–6338.

    Article  CAS  PubMed  Google Scholar 

  2. Laubach J, Richardson P, Anderson K . Multiple myeloma. Annu Rev Med 2011; 62: 249–264.

    Article  CAS  PubMed  Google Scholar 

  3. Pineda-Roman M, Zangari M, Haessler J, Anaissie E, Tricot G, van Rhee F et al. Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol 2008; 140: 625–634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. San Miguel JF, Mateos M-V . Can multiple myeloma become a curable disease? Haematologica 2011; 96: 1246–1248.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fonseca R . Strategies for risk-adapted therapy in myeloma. Hematol Am Soc Hematol Educ Program 2007, 304–310.

    Article  Google Scholar 

  6. Stewart AK, Fonseca R . Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol 2005; 23: 6339–6344.

    Article  CAS  PubMed  Google Scholar 

  7. Shaughnessy JDJ, Zhan F, Burington BE, Huang Y, Colla S, Hanamura I et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 2006; 109: 2276–2284.

    Article  PubMed  Google Scholar 

  8. Shaughnessy JD, Qu P, Usmani S, Heuck CJ, Zhang Q, Zhou Y et al. Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3. Blood 2011; 118: 3512–3524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kuiper R, Broyl A, de Knegt Y, van Vliet MH, van Beers EH, van der Holt B et al. A gene expression signature for high-risk multiple myeloma. Leukemia 2012; 26: 2406–2413.

    Article  CAS  PubMed  Google Scholar 

  10. Chung T-H, Mulligan G, Fonseca R, Chng W-J . A novel measure of chromosome instability can account for prognostic difference in multiple myeloma. PLoS One 2013; 8: e66361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chng W-J, Braggio E, Mulligan G, Bryant B, Remstein E, Valdez R et al. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood 2008; 111: 1603–1609.

    Article  CAS  PubMed  Google Scholar 

  12. Moreaux J, Klein B, Bataille R, Descamps G, Maiga S, Hose D et al. A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines. Haematologica 2011; 96: 574–582.

    Article  CAS  PubMed  Google Scholar 

  13. Dickens NJ, Walker BA, Leone PE, Johnson DC, Brito JL, Zeisig A et al. Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome. Clin Cancer Res 2010; 16: 1856–1864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Decaux O, Lode L, Magrangeas F, Charbonnel C, Gouraud W, Jezequel P et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myelome. J Clin Oncol 2008; 26: 4798–4805.

    Article  CAS  PubMed  Google Scholar 

  15. Hose D, Reme T, Hielscher T, Moreaux J, Messner T, Seckinger A et al. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma. Haematologica 2011; 96: 87–95.

    Article  PubMed  Google Scholar 

  16. Barrett T, Keats JJ, Mittal V, Delmore JE, Zhang MQ, Moreau P et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res 2013; 41: D991–D995.

    Article  CAS  PubMed  Google Scholar 

  17. Mulligan G, Mitsiades C, Bryant B, Zhan F, Chng W-J, Roels S et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood 2007; 109: 3177–3188.

    Article  CAS  PubMed  Google Scholar 

  18. Bair E, Bourne PE, Weinmann AS, Chibon F, Smith AV, Nadon R et al. Prediction by supervised principal components. J Amer Statist Assoc 2006; 101: 119–137.

    Article  CAS  Google Scholar 

  19. R Library: MMGEP. Available from http://figshare.com/s/05c4814ca07d11e4872a06ec4bbcf141 (accessed 9 November 2015).

  20. R Library: MMGeneSigIndex. Available from http://figshare.com/s/580fd96aa07d11e4948106ec4b8d1f61 (accessed 9 November 2015).

  21. Bair E, Tibshirani R . Semi-supervised methods to predict patient survival from gene expression data. PLoS Biol 2004; 2: e108.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhao X, Rødland EA, Sørlie T, Naume B, Langerød A, Frigessi A et al. Combining gene signatures improves prediction of breast cancer survival. PLoS One 2011; 6: e17845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Reyal F, Kerr MK, Maiso P, Tesarova L, Jiang J, Liu H et al. A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer. Breast Cancer Res 2008; 10: 1–15.

    Article  Google Scholar 

  24. Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, Haibe-Kains B et al. Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 2008; 10: R65–11.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Buffa FM, Harris AL, West CM, Miller CJ . Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer 2010; 102: 428–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Abba MC, Lacunza E, Butti M, Aldaz CM . Breast cancer biomarker discovery in the functional genomic age: a systematic review of 42 gene expression signatures. Biomark Insights 2010; 5: 103–118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Durie BG, Salmon SE . A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842–854.

    Article  CAS  PubMed  Google Scholar 

  28. Greipp PR, San Miguel J, Durie BGM, Crowley JJ, Barlogie B, Bladé J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.

    Article  PubMed  Google Scholar 

  29. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007; 109: 3489–3495.

    Article  CAS  PubMed  Google Scholar 

  30. Avet-Loiseau H, Durie BGM, Cavo M, Attal M, Gutierrez N, Haessler J et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia 2013; 27: 711–717.

    Article  CAS  PubMed  Google Scholar 

  31. Chng W-J, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014; 28: 269–277.

    Article  CAS  PubMed  Google Scholar 

  32. Kuiper R, van Duin M, van Vliet MH, Broijl A, van der Holt B, Jarari el L et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood 2015; 126: 1996–2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. W J Chng, T-H Chung, S Kumar, S Usmani, N Munshi, H Avet-Loiseau, H Goldschmidt, B Durie and P Sonneveld: W J Chng and T-H Chung: These authors contributed equally to this work.

  2. The members of International Myeloma working Group are listed before the references.

Authors and Affiliations

  1. Cancer Science Institute, National University of Singapore, Singapore, Singapore,

    W J Chng

  2. National University Cancer Institute of Singapore, National University Health System, Singapore, Singapore

    T-H Chung

  3. Department of Hematology, Mayo Clinic, MN, USA

    S Kumar

  4. Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC, USA

    S Usmani

  5. Dana-Farber Cancer Institute, Boston, MA, USA

    N Munshi

  6. Unité de Génomique du Myélome, University of Toulouse, Toulouse, France

    H Avet-Loiseau

  7. University Hospital Heidelberg, Heidelberg, Germany

    H Goldschmidt

  8. Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA, USA

    B Durie

  9. Erasmus MC, Rotterdam, The Netherlands

    P Sonneveld

Authors
  1. W J Chng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T-H Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Usmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Munshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Avet-Loiseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Goldschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B Durie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P Sonneveld
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the International Myeloma Working Group

Corresponding author

Correspondence to W J Chng.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

International Myeloma Working Group

Niels Abildgaard1, Rafat Abonour2, Melissa Alsina3, Kenneth C Anderson4, Michel Attal5, Hervé Avet-Loiseau6, Ashraf Badros7, Nizar Jacques Bahlis8, Bart Barlogie9, Régis Bataille10, Meral Beksaç11, Andrew Belch12, Dina Ben-Yehuda13, Bill Bensinger14, P Leif Bergsagel15, Manisha Bhutani16, Jenny Bird17, Joan Bladé18, Annemiek Broijl19, Mario Boccadoro20, Jo Caers21, Michele Cavo22, Asher Chanan-Khan23, Ajai Chari24, Wen Ming Chen25, Marta Chesi26, J Anthony Child27, Chor Sang Chim28, Wee-Joo Chng29, Ray Comenzo30, Gordon Cook31, John Crowley32, Edvan Crusoe33, William Dalton34, Faith Davies35, Javier de la Rubia36, Cármino de Souza37, Michel Delforge38, Madhav Dhodapkar39, Meletios Dimopoulos40, Angela Dispenzieri41, Johannes Drach42, Matthew Drake43, Juan Du44, Brian GM Durie45, Hermann Einsele46, Theirry Facon47, Dorotea Fantl48, Jean-Paul Fermand49, Carlos Fernández de Larrea50, Rafael Fonseca51, Gösta Gahrton52, Ramón García-Sanz53, Laurent Garderet54, Christina Gasparetto55, Morie Gertz56, Irene Ghobrial57, John Gibson58, Peter Gimsing59, Sergio Giralt60, Hartmut Goldschmidt61, Jingli Gu62, Roman Hajek63, Izhar Hardan64, Parameswaran Hari65, Hiroyuki Hata66, Yutaka Hattori67, Tom Heffner68, Jens Hillengass69, Joy Ho70, Antje Hoering71, Jian Hou72, Jeffrey Huang73, Vania Hungria74, Shinsuke Ida75, Sundar Jagannath76, Andrzej J Jakubowiak77, Hans Johnsen78, Douglas Joshua79, Artur Jurczyszyn80, Martin Kaiser81, Efstathios Kastritis82, Jonathan Kaufman83, Michio Kawano84, Neha Korde85, Eva Kovacs86, Amrita Krishnan87, Sigurdur Kristinsson88, Nicolaus Kröger89, Shaji Kumar90, Robert A Kyle91, Chara Kyriacou92, Martha Lacy93, Juan José Lahuerta94, Ola Landgren95, Alessandra LaRocca96, Jacob Laubach97, Fernando Leal da Costa98, Jae-Hoon Lee99, Merav Leiba100, Xavier Leleu101, Suzanne Lentzsch102, Nelson Leung103, Henk Lokhorst104, Sagar Lonial105, Jin Lu106, Heinz Ludwig107, Anuj Mahindra108, Angelo Maiolino109, Elisabet E Manasanch110, Tomer Mark111, María-Victoria Mateos112, Amitabha Mazumder113, Philip McCarthy114, Jayesh Mehta115, Ulf-Henrik Mellqvist116, Giampaolo Merlini117, Joseph Mikhael118, Philippe Moreau119, Gareth Morgan120, Nikhil Munshi121, Hareth Nahi122, Weerasak Nawarawong123, Ruben Niesvizky124, Amara Nouel125, Yana Novis126, Michael O’Dwyer127, Peter O’Gorman128, Enrique Ocio129, Alberto Orfao130, Robert Orlowski131, Paula Rodriguez Otero132, Bruno Paiva133, Antonio Palumbo134, Santiago Pavlovsky135, Linda Pilarski136, Raymond Powles137, Guy Pratt138, Lugui Qui139, Noopur Raje140, S Vincent Rajkumar141, Donna Reece142, Anthony Reiman143, Paul G Richardson144, Joshua Richter145, Angelina Rodríguez Morales146, Kenneth R Romeril147, David Roodman148, Laura Rosiñol149, Adriana Rossi150, Murielle Roussel151, Stephen Russell152, Jesús San Miguel153, Rik Schots154, Sabina Sevcikova155, Orhan Sezer156, Jatin J Shah157, Kazuyuki Shimizu158, Chaim Shustik159, David Siegel160, Seema Singhal161, Pieter Sonneveld162, Andrew Spencer163, Edward Stadtmauer164, Keith Stewart165, Daryl Tan166, Evangelos Terpos167, Patrizia Tosi168, Guido Tricot169, Ingemar Turesson170, Saad Usmani171, Ben Van Camp172, Brian Van Ness173, Ivan Van Riet174, Isabelle Vande Broek175, Karin Vanderkerken176, Robert Vescio177, David Vesole178, Ravi Vij179, Peter Voorhees180, Anders Waage181, Michael Wang182, Donna Weber183, Brendan M Weiss184, Jan Westin185, Keith Wheatley186, Elena Zamagni187, Jeffrey Zonder188, Sonja Zweegman189

1Syddansk Universitet, Odense, Denmark; 2Indiana University School of Medicine, Indianapolis, Indiana, USA; 3H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA; 4Dana-Farber Cancer Institute, Boston, Massachusetts, USA; 5Purpan Hospital, Toulouse, France; 6University of Toulouse, Toulouse, France; 7University of Maryland, Baltimore, Maryland, USA; 8University of Calgary, Calgary, Canada; 9M.I.R.T. UAMS Little Rock, Arkanas, USA; 10Institute de Biologie, Nantes, France; 11Ankara University, Ankara, Turkey; 12University of Alberta, Alberta, Canada; 13Hadassah University Hospital, Hadassah, Israel; 14Fred Hutchinson Cancer Center, Seattle, Washington, USA; 15Mayo Clinic Scottsdale, Scottsdale, Arizona, USA; 16Carolinas Healthcare System, Charlotte, North Carolina, USA; 17Bristol Haematology and Oncology Centre, Bristol, United Kingdom; 18Hospital Clinica, Barcelona, Spain; 19Erasmus MC, Rotterdam, The Netherlands; 20University of Torino, Torino, Italy; 21Centre Hospitalier Universitaire de Liège, Liège, Belgium; 22Universita di Bologna, Bologna, Italy; 23Mayo Clinic, Jacksonville, Florida, USA; 24Mount Sinai Medical Center, New York, NY, USA; 25Beijing Chaoyang Hospital, Beijing, China; 26Mayo Clinic Scottsdale, Scottsdale, Arizona, USA; 27Leeds General Hospital, Leeds, United Kingdom; 28Department of Medicine, Queen Mary Hospital, Hong Kong; 29National University Health System, Singapore; 30Tufts Medical School, Boston, Massachusetts, USA; 31University of Leeds, United Kingdom; 32Cancer Research and Biostatistics, Seattle, Washington, USA; 33Faculdade de Ciências Médicas da Santa Casa de São Paulo, Brazil; 34H. Lee Moffitt, Tampa, Florida, USA; 35University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; 36Hospital Universitario La Fe, Valencia, Spain; 37Univeridade de Campinas, Caminas, Brazil; 38University Hospital Gasthuisberg, Leuven, Belgium; 39Yale Cancer Center, New Haven, CT, USA; 40University of Athens School of Medicine, Athens, Greece; 41Mayo Clinic, Rochester, Minnesota, USA; 42University of Vienna, Vienna, Austria; 43Mayo Clinic Rochester, Rochester, Minnesota, USA; 44Changzhen Hospital, Shanghai China; 45Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, California, USA; 46Universitätsklinik Würzburg, Würzburg, Germany; 47Centre Hospitalier Regional Universitaire de Lille, Lille, France; 48Socieded Argentinade Hematolgia, Buenos Aires, Argentina; 49Hopital Saint-Louis, Paris, France; 50Hospital Clínic de Barcelona, Barcelona, Spain; 51Mayo Clinic Scottsdale, Scottsdale, Arizona, USA; 52Karolinska Institute for Medicine, Huddinge, Sweden; 53University Hospital of Salamanca, Salamanca, Spain; 54Hopital Saint Antoine, Paris, France; 55Duke University Medical Center, Durham, North Carolina, USA; 56Mayo Clinic, Rochester, Minnesota, USA; 57Dana-Farber Cancer Institute, Boston, MA, USA; 58Royal Prince Alfred Hospital, Sydney, Australia; 59University of Copenhagen, Copenhagen, Denmark; 60Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 61University Hospital Heidelberg, Heidelberg, Germany; 62The First Hospital, Sun Yat-Sen University, Guangdong, China; 63University Hospital Ostrava and School of Medicine OU, Ostrava, Czech Republic; 64Tel Aviv University, Tel Aviv, Israel; 65Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 66Kumamoto University Hospital, Kumamoto, Japan; 67Keio University School of Medicine, Tokyo, Japan; 68Emory University, Atlanta, Georgia, USA; 69University of Heidelberg, Heidelberg, Germany; 70Royal Prince Alfred Hospital, Sydney, Australia; 71Cancer Research and Biostatistics, Seattle, WA, USA; 72Shanghai Chang Zheng Hospital, Shanghai, China; 73National Taiwan University Hospital, Taiwan; 74Clinica San Germano, Sao Paolo, Brazil; 75Nagoya City University Medical School, Nagoya, Japan; 76Mt. Sinai Cancer Institute, New York, New York, USA; 77University of Chicago, Chicago, Illinois, USA; 78Aalborg Hospital Science and Innovation Center, Aalborg, Denmark; 79Royal Prince Alfred Hospital, Sydney, Australia; 80University Hospital, Cracow, Poland; 81Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 82University of Athens, Athens, Greece; 83Emory Clinic, Atlanta, Georgia, USA; 84Yamaguchi University, Ube, Japan; 85National Institutes of Health, Bethesda, Maryland, USA; 86Cancer Immunology Research-Life, Birsfelden, Switzerland; 87City of Hope, Duarte, California, USA; 88Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; 89University Hospital Hamburg, Hamburg, Germany; 90Department of Hematology, Mayo Clinic, Minnesota, USA; 91Department of Laboratory Med. and Pathology, Mayo Clinic, Minnesota, USA; 92Northwick Park Hospital, London, United Kingdom; 93Mayo Clinic Rochester, Rochester, Minnesota, USA; 94Grupo Español di Mieloma, Hospital Universitario 12 de Octubre, Madrid, Spain; 95Memorial Sloan Kettering Cancer Center, New York, New York, USA; 96Divisione Universitaria di Ematologia, Torino, Itay; 97Dana-Farber Cancer Institute, Boston, Massachusetts, USA; 98Instituto Portugues De Oncologia, Lisbon, Portugal; 99Gachon University Gil Hospital, Incheon, Korea; 100Sheba Medical Center, Tel Hashomer, Israel; 101Hospital Huriez, CHRU Lille, France; 102Columbia University, New York, New York, USA; 103Mayo Clinic Rochester, Rochester, MN, USA; 104University Medical Center Utrecht, Utrecht, The Netherlands; 105Emory University Medical School, Atlanta, Georgia, USA; 106Peoples Hospital, Beijing University, Beijing, China; 107Wilhelminenspital Der Stat Wien, Vienna, Austria; 108University of California, San Francisco, San Francisco, California, USA; 109Rua fonte da Saudade, Rio de Janeiro, Brazil; 110MD Anderson Cancer Center, Houston, Texas, USA; 111Weill Cornell Medical College, New York, New York, USA; 112University Hospital of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain; 113NYU Comprehensive Cancer Center, New York, New York, USA; 114Roswell Park Cancer Center, Buffalo, New York, USA; 115Northwestern University, Chicago, Illinois, USA; 116Sahlgrenska University Hospital, Gothenburg, Sweden; 117University of Pavia, Pavia, Italy; 118Mayo Clinic Arizona, Scottsdale, Arizona, USA; 119University Hospital, Nantes, France; 120University of Arkansas for Medical Sciences, MyelomaInstitute for Research and Therapy, Little Rock, Arkansas, USA; 121Dana-Farber Cancer Institute, Boston, Massachusetts, USA; 122Karolinska University Hospital, Stockholm, Sweden; 123Chiang Mai University, Thailand; 124Weill Cornell Medical College, New York, New York, USA; 125Hospital Rutz y Paez, Bolivar, Venezuela; 126Hospital Sírio Libanês, Bela Vista, Brazil; 127National University of Ireland, Ireland; 128Mater University Hospital, Ireland; 129University Hospital of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain; 130University Hospital of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain; 131MD Anderson Cancer Center, Houston, Texas, USA; 132Clinica Universidad de Navarra, Navarra, Spain; 133Clinica Universitaria de Navarra, CIMA, Pamplona, Spain; 134University of Torino, Torino, Italy; 135Fundaleu, Buenos Aires, Argentina; 136University of Alberta, Alberta, Canada; 137Parkside Cancer Centre, London, England; 138Heart of England NHS Foundation Trust, England, United Kingdom; 139Institute of Hematology and Blood Diseases, Tianjin, China; 140Massachusetts General Hospital, Boston, Massachusetts, USA; 141Mayo Clinic, Rochester, Minnesota, USA; 142Princess Margaret Hospital, Toronto, Canada; 143Saint John Regional Hospital, Saint John, New Brunswick, Canada; 144Dana-Farber Cancer Institute, Boston, Massachusetts, USA; 145Hackensack University Medical Center, Hackensack, New Jersey, USA; 146Bonco Metro Politano de Sangre, Caracas, Venezuela; 147Wellington Hospital, Wellington, New Zealand; 148Indiana University, Indianapolis, Indiana, USA; 149Hospital Clinic, Barcelona, Spain; 150Weill Cornell Medical College, New York, New York, USA; 151University of Toulouse, Toulouse, France; 152Mayo Clinic, Rochester, Minnesota, USA; 153Clinica Universitaria de Navarra, CIMA, Pamplona, Spain; 154Universitair Ziekenhuis Brussel, Brussels, Belgium; 155Masaryk University, Brno, Czech Republic; 156Memorial Sisli Hastanesi, Istanbul, Turkey; 157MD Anderson Cancer Center, Houston, Texas, USA; 158Tokai Central Hospital, Kakamigahara, Japan; 159McGill University, Montreal, Canada; 160Hackensack University Medical Center, Hackensack, New Jersey, USA; 161Northwestern University, Chicago, Illinois, USA; 162Erasmus MC, Rotterdam, The Netherlands; 163The Alfred Hospital, Melbourne, Australia; 164University of Pennsylvania, Philadelphia, Pennsylvania, USA; 165Mayo Clinic Arizona, Scottsdale, Arizona, USA; 166Singapore General Hospital, Singapore; 167University of Athens School of Medicine, Athens, Greece; 168Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy; 169University of Iowa Hospital and Clinics, Iowa City, Iowa, USA; 170SKANE University Hospital, Malmo, Sweden; 171Levine Cancer Institute/Carolinas Healthcare System, Charlotte, North Carolina, USA; 172Vrije Universiteit Brussels, Brussels, Belgium; 173University of Minnesota, Minneapolis, Minnesota, USA; 174Brussels Vrije University, Brussels, Belgium; 175Vrije Universiteit Brussels, Brussels, Belgium; 176Vrije University Brussels VUB, Brussels, Belgium; 177Cedars-Sinai Cancer Center, Los Angeles, California, USA; 178Hackensack University Medical Center, Hackensack, New Jersey, USA; 179Washington University School of Medicine, St. Louis, MO, USA; 180University of North Carolina, Chapel Hill, North Carolina, USA; 181University Hospital, Trondheim, Norway NSMG; 182MD Anderson Cancer Center, Houston, Texas, USA; 183MD Anderson Cancer Center, Houston, Texas, USA; 184Abramson Cancer Center, Philadelphia, Pennsylvania, USA; 185Sahlgrenska University Hospital, Gothenburg, Sweden; 186University of Birmingham, Birmingham, United Kingdom; 187University of Bologna, Bologna, Italy; 188Karmanos Cancer Institute, Detroit, Michigan, USA; 189VU University Medical Center, Amsterdam, The Netherlands

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chng, W., Chung, TH., Kumar, S. et al. Gene signature combinations improve prognostic stratification of multiple myeloma patients. Leukemia 30, 1071–1078 (2016). https://doi.org/10.1038/leu.2015.341

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2015.341

This article is cited by

Search

Advanced search

Quick links