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

Michela Mattioli, Luca Agnelli, Sonia Fabris, Luca Baldini, Fortunato Morabito, Silvio Bicciato, Donata Verdelli, Daniela Intini, Lucia Nobili, Lilla Cro, Giancarlo Pruneri, Vincenzo Callea, Caterina Stelitano, Anna Teresa Maiolo, Luigia Lombardi, Antonino Neri

Research output: Contribution to journalArticlepeer-review

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, MUS) 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.

Original languageEnglish
Pages (from-to)2461-2473
Number of pages13
JournalOncogene
Volume24
Issue number15
DOIs
Publication statusPublished - Apr 7 2005

Keywords

  • Gene expression profiling
  • IGH translocations
  • MGUS
  • Multiple myeloma
  • Plasma cell leukemia

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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