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Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-11-3385.
Submitted November 7, 2002
Accepted February 15, 2003
Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease
Florence Magrangeas, Valery Nasser, Herve Avet-Loiseau, Beatrice Loriod, Olivier Decaux, Samuel Granjeaud, Francois Bertucci, Daniel Birnbaum, Catherine Nguyen, Jean-Luc Harousseau, Regis Bataille, Remi Houlgatte, and Stephane Minvielle*
Unite 463, INSERM, Nantes, France
ERM206, INSERM, Marseille, France
United 119, INSERM, Marseille, France
Department of Clinical Hematology, University Hospital, Nantes, France
* Corresponding author; email: sminviel{at}nantes.inserm.fr.
Although multiple myeloma (MM) is a unique entity, a marked heterogeneity is actually observed among the patients, which has been first related to immunoglobulin (Ig) types and light chain subtypes, and more recently to chromosomal abnormalities. In order to further investigate this genetic heterogeneity, we analyzed gene expression profiles of 92 primary tumors according to their Ig types and light chain subtypes with DNA microarrays. Several clusters of genes involved in various biological functions such as immune response, cell cycle control, signaling, apoptosis, cell adhesion and structure significantly discriminated IgA- from IgG-MM. Genes associated with inhibition of differentiation and apoptosis induction were up-regulated while genes associated with immune response, cell cycle control and apoptosis were down-regulated in IgA-MM. According to the expression of the 61 most discriminating genes, BJ-MM represented a separate subgroup that did not express either the genes characteristic of IgG-MM, or those of IgA-MM at a high level. This suggests that transcriptional programs associated to the switch could be maintained up to plasma cell differentiation. Several genes whose products are known to stimulate bone remodeling discriminate between  and  MM. One of these genes, Mip-1 , was overexpressed in the subgroup. In addition we established a strong association (P=.0001) between subgroup expressing high levels of Mip-1 and active myeloma bone disease. This study shows that DNA microarrays enable to perform a molecular dissection of the bioclinical diversity of MM and provides new molecular tools to investigate the pathogenesis of malignant plasma cells.
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