Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients

Annemiek Broyl, Dirk Hose, Henk Lokhorst, Yvonne de Knegt, Justine Peeters, Anna Jauch, Uta Bertsch, Arjan Buijs, Marian Stevens-Kroef, H. Berna Beverloo, Edo Vellenga, Sonja Zweegman, Marie-Josée Kersten, Bronno van der Holt, Laila el Jarari, George Mulligan, Hartmut Goldschmidt, Mark van Duin, Pieter Sonneveld

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Abstract

To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities
Original languageEnglish
Pages (from-to)2543-2553
JournalBlood
Volume116
Issue number14
DOIs
Publication statusPublished - 2010

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