Originally published as JCO Early Release 10.1200/JCO.2007.13.8545 on June 30 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Decaux, O. Articles by Minvielle, S. Search for Related Content PubMed PubMed Citation Articles by Decaux, O. Articles by Minvielle, S. Social Bookmarking                            What's this?

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 Myélome

Olivier Decaux, Laurence Lodé, Florence Magrangeas, Catherine Charbonnel, Wilfried Gouraud, Pascal Jézéquel, Michel Attal, Jean-Luc Harousseau, Philippe Moreau, Régis Bataille, Loïc Campion, Hervé Avet-Loiseau, Stéphane Minvielle

From L'Institut National de la Santé et de la Recherche Médicale, U892, University of Nantes; University, Hospital, Hematology Laboratory, Nantes; Centre de Lutte contre le Cancer Nantes Atlantique, Nantes-Saint Herblain; and University, Hospital, Hematology Department, Toulouse, France

Corresponding author: Stéphane Minvielle, MD, INSERM U892 Institute of Biology, 9 Quai Moncousu, Nantes 44093, France; e-mail: sminvielle{at}chu-nantes.fr

Purpose Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers.

Patients and Methods In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival. A survival model was built from these genes. The validity of our model was assessed in our test set of 68 patients and in three independent cohorts comprising 853 patients with multiple myeloma.

Results The 15 strongest genes associated with the length of survival were used to calculate a risk score and to stratify patients into low-risk and high-risk groups. The survival-predictor score was significantly associated with survival in both the training and test sets and in the external validation cohorts. The Kaplan-Meier estimates of rates of survival at 3 years were 90.5% (95% CI, 85.6% to 95.3%) and 47.4% (95% CI, 33.5% to 60.1%), respectively, in our patients having a low risk or high risk independently of traditional prognostic factors. High-risk patients constituted a homogeneous biologic entity characterized by the overexpression of genes involved in cell cycle progression and its surveillance, whereas low-risk patients were heterogeneous and displayed hyperdiploid signatures.

Conclusion Gene expression–based survival prediction and molecular features associated with high-risk patients may be useful for developing prognostic markers and may provide basis to treat these patients with new targeted antimitotics.

published online ahead of print at www.jco.org on June 30, 2008

Supported in part by grants from the International Myeloma Foundation, the Ligue contre le Cancer (Equipe Labellisée), and the Cancéropôle Grand Ouest.

L.C., H.A.L., and S.M. contributed equally to this work.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				H. Avet-Loiseau, C. Li, F. Magrangeas, W. Gouraud, C. Charbonnel, J.-L. Harousseau, M. Attal, G. Marit, C. Mathiot, T. Facon, et al. Prognostic Significance of Copy-Number Alterations in Multiple Myeloma J. Clin. Oncol., September 20, 2009; 27(27): 4585 - 4590. [Abstract] [Full Text] [PDF]

				J.-L. Harousseau and P. Moreau Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma N. Engl. J. Med., June 18, 2009; 360(25): 2645 - 2654. [Full Text] [PDF]