Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease
| Autor: | Hervé Avet-Loiseau, Régis Bataille, Florence Magrangeas, Harousseau Jl, Samuel Granjeaud, Stephane Minvielle, Olivier Decaux, Béatrice Loriod, Daniel Birnbaum, Catherine Nguyen, Rémi Houlgatte, Valéry Nasser, François Bertucci |
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| Přispěvatelé: | Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU) |
| Rok vydání: | 2003 |
| Předmět: |
Adult
[SDV]Life Sciences [q-bio] Genes MHC Class II Plasma Cells Immunology Apoptosis Immunoglobulin light chain Biochemistry Immunoglobulin kappa-Chains 03 medical and health sciences 0302 clinical medicine Immunoglobulin lambda-Chains Plasma cell differentiation Gene expression Cell Adhesion Humans Chemokine CCL4 Gene ComputingMilieux_MISCELLANEOUS Aged Chemokine CCL3 Oligonucleotide Array Sequence Analysis 030304 developmental biology Gene Rearrangement 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction Genetic heterogeneity Gene Expression Profiling Cell Biology Hematology Macrophage Inflammatory Proteins Middle Aged Molecular biology Immunoglobulin A Genes cdc Gene expression profiling Immunoglobulin G 030220 oncology & carcinogenesis biology.protein DNA microarray Antibody Immunoglobulin Heavy Chains Multiple Myeloma Signal Transduction |
| Zdroj: | Blood Blood, 2003, 101 (12), pp.4998-5006. ⟨10.1182/blood-2002-11-3385⟩ Blood, American Society of Hematology, 2003, 101 (12), pp.4998-5006. ⟨10.1182/blood-2002-11-3385⟩ |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2002-11-3385 |
| Popis: | 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 κ- and λ-MM. One of these genes, Mip-1α, was overexpressed in the κ subgroup. In addition, we established a strong association (P = .0001) between κ subgroup expressing high levels of Mip-1α 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. |
| Databáze: | OpenAIRE |
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