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

Oncogene volume 24, pages 2461–2473 (2005)Cite this article

Abstract

Multiple myeloma (MM) is the most common form of plasma cell dyscrasia, characterized by a marked heterogeneity of genetic lesions and clinical course. It may develop from a premalignant condition (monoclonal gammopathy of undetermined significance, MGUS) or progress from intramedullary to extramedullary forms (plasma cell leukemia, PCL). To provide insights into the molecular characterization of plasma cell dyscrasias and to investigate the contribution of specific genetic lesions to the biological and clinical heterogeneity of MM, we analysed the gene expression profiles of plasma cells isolated from seven MGUS, 39 MM and six PCL patients by means of DNA microarrays. MMs resulted highly heterogeneous at transcriptional level, whereas the differential expression of genes mainly involved in DNA metabolism and proliferation distinguished MGUS from PCLs and the majority of MM cases. The clustering of MM patients was mainly driven by the presence of the most recurrent translocations involving the immunoglobulin heavy-chain locus. Distinct gene expression patterns have been found to be associated with different lesions: the overexpression of CCND2 and genes involved in cell adhesion pathways was observed in cases with deregulated MAF and MAFB, whereas genes upregulated in cases with the t(4;14) showed apoptosis-related functions. The peculiar finding in patients with the t(11;14) was the downregulation of the α-subunit of the IL-6 receptor. In addition, we identified a set of cancer germline antigens specifically expressed in a subgroup of MM patients characterized by an aggressive clinical evolution, a finding that could have implications for patient classification and immunotherapy.

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Acknowledgements

This work was supported by grants from the Associazione Italiana Ricerca sul Cancro (to AN), Ministero della Salute; Ministero dell'Universita' e Ricerca Scientifica (FIRB projects RBAU012E9A to AN, RBNE01TZZ8 and RBAU01935A to SB) and Associazione Studio Malati Ematologici, Milano.

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Author notes

  1. Michela Mattioli and Luca Agnelli: These two authors contributed equally to this work

Authors and Affiliations

  1. Laboratorio di Ematologia Sperimentale e Genetica Molecolare and U.O. Ematologia 1, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS, Milano, Italy

    Michela Mattioli, Luca Agnelli, Sonia Fabris, Luca Baldini, Donata Verdelli, Daniela Intini, Lucia Nobili, Lilla Cro, Anna Teresa Maiolo, Luigia Lombardi & Antonino Neri

  2. Divisione di Ematologia and Centro Trapianto di Midollo, Azienda Ospedaliera ‘Bianchi-Melacrinò-Morelli’, Reggio Calabria, Italy

    Fortunato Morabito, Vincenzo Callea & Caterina Stelitano

  3. Dipartimento dei Processi Chimici dell'Ingegneria, Università di Padova, Padova, Italy

    Silvio Bicciato

  4. Divisione di Patologia, Istituto Europeo di Oncologia, Milano, Italy

    Giancarlo Pruneri

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  1. Michela Mattioli
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Correspondence to Antonino Neri.

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Mattioli, M., Agnelli, L., Fabris, S. et al. Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma. Oncogene 24, 2461–2473 (2005). https://doi.org/10.1038/sj.onc.1208447

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