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

A. Broijl, D Hose, H Lokhorst, Yvonne Knegt, Justine Peeters, A Jauch, U Bertsch, Pieter Sonneveld, A Buijs, M Stevens-Kroef, Berna Beverloo, E Vellenga, S Zweegman, MJ Kersten, Ronnie van der Holt, L (Laila) Jarari, G Mulligan, H Goldschmidt, Mark van Duin

Research output: Contribution to journalArticleAcademicpeer-review

247 Citations (Scopus)


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. An-other 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. (Blood. 2010;116(14):2543-2553)
Original languageUndefined/Unknown
Pages (from-to)2543-2553
Number of pages11
Issue number14
Publication statusPublished - 2010

Research programs

  • EMC MGC-02-96-01
  • EMC MM-02-41-03

Cite this