Introduction: Multiple Myeloma (MM) is characterized by genetic heterogeneity and varied clinical course. MM may develop from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS) and progress to plasma cell leukemia (PCL). Chromosomal translocations involving the immunoglobulin heavy-chain locus (IGH) and a promiscuous array of partner loci represent early and frequent genetic aberrations in MM.Methods: The gene expression profiles of purified plasma cells isolated from 7 MGUS, 39 MM and 6 PCL patients were analyzed by DNA microarrays, to investigate the molecular characterization of MM and the contribution of specific genetic lesions to the biological and clinical variability of MM.Results: MGUS patients could be distinguished from PCLs and the majority of MMs, while MMs were characterized by highly heterogeneous phenotype, being mainly grouped according to the presence of the most recurrent IGH translocations and specific gene expression signatures associated with each lesions. Overexpression of CCND2 and genes involved in cell-adhesion pathways in patients with dysregulated MAF and MAFB, upregulation of genes with apoptosis-related functions in t(4;14) patients and downregulation of the IL6-R in t(11;14) patients were identified. In addition, a group of MM patients with aggressive clinical evolution is characterized by a set of cancer germ line-specific antigens, a finding that could have implications for patients’ classification and immunotherapy in MM.Conclusions: Our study supports the notion of a marked heterogeneity of MM and provides insights into the role of distinct molecular pathways in MM.

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma / Mattioli, M; Agnelli, L; Fabris, S; Baldini, L; Morabito, F; Bicciato, Silvio; Verdelli, D; Nobili, L; Intini, D; Callea, V; Lombardi, L; Neri, A.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 16:(2005), pp. 167-167. ((Intervento presentato al convegno 9th International Conference on Malignant Lymphoma tenutosi a Lugano (Svizzera) nel 7-11 Giugno 2005.

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma

BICCIATO, Silvio;
2005

Abstract

Introduction: Multiple Myeloma (MM) is characterized by genetic heterogeneity and varied clinical course. MM may develop from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS) and progress to plasma cell leukemia (PCL). Chromosomal translocations involving the immunoglobulin heavy-chain locus (IGH) and a promiscuous array of partner loci represent early and frequent genetic aberrations in MM.Methods: The gene expression profiles of purified plasma cells isolated from 7 MGUS, 39 MM and 6 PCL patients were analyzed by DNA microarrays, to investigate the molecular characterization of MM and the contribution of specific genetic lesions to the biological and clinical variability of MM.Results: MGUS patients could be distinguished from PCLs and the majority of MMs, while MMs were characterized by highly heterogeneous phenotype, being mainly grouped according to the presence of the most recurrent IGH translocations and specific gene expression signatures associated with each lesions. Overexpression of CCND2 and genes involved in cell-adhesion pathways in patients with dysregulated MAF and MAFB, upregulation of genes with apoptosis-related functions in t(4;14) patients and downregulation of the IL6-R in t(11;14) patients were identified. In addition, a group of MM patients with aggressive clinical evolution is characterized by a set of cancer germ line-specific antigens, a finding that could have implications for patients’ classification and immunotherapy in MM.Conclusions: Our study supports the notion of a marked heterogeneity of MM and provides insights into the role of distinct molecular pathways in MM.
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Mattioli, M; Agnelli, L; Fabris, S; Baldini, L; Morabito, F; Bicciato, Silvio; Verdelli, D; Nobili, L; Intini, D; Callea, V; Lombardi, L; Neri, A.
Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma / Mattioli, M; Agnelli, L; Fabris, S; Baldini, L; Morabito, F; Bicciato, Silvio; Verdelli, D; Nobili, L; Intini, D; Callea, V; Lombardi, L; Neri, A.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 16:(2005), pp. 167-167. ((Intervento presentato al convegno 9th International Conference on Malignant Lymphoma tenutosi a Lugano (Svizzera) nel 7-11 Giugno 2005.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/421443
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