title: Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease.
abstract: 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. 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 biologic 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 kappa- and lambda-MM. One of these genes, Mip-1alpha, was overexpressed in the kappa subgroup. In addition, we established a strong association (P =.0001) between kappa subgroup expressing high levels of Mip-1alpha and active myeloma bone disease. This study shows that DNA microarrays enable us to perform a molecular dissection of the bioclinical diversity of MM and provide new molecular tools to investigate the pathogenesis of malignant plasma cells.
authors.affiliation: INSERM U463, Department of Clinical Hematology, University Hospital, Nantes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Magrangeas
authors.forename: Valéry
authors.initials: V
authors.lastname: Nasser
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Béatrice
authors.initials: B
authors.lastname: Loriod
authors.forename: Olivier
authors.initials: O
authors.lastname: Decaux
authors.forename: Samuel
authors.initials: S
authors.lastname: Granjeaud
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Catherine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Régis
authors.initials: R
authors.lastname: Bataille
authors.forename: Rémi
authors.initials: R
authors.lastname: Houlgatte
authors.forename: Stéphane
authors.initials: S
authors.lastname: Minvielle
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D005802:Genes, MHC Class II; D018816:Genes, cdc; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D019402:Macrophage Inflammatory Proteins