The molecular classification of multiple myeloma

Fenghuang Zhan, Yongsheng Huang, Simona Colla, James P. Stewart, Ichiro Hanamura, Sushil Gupta, Joshua Epstein, Shmuel Yaccoby, Jeffrey Sawyer, Bart Burington, Elias Anaissie, Klaus Hollmig, Mauricio Pineda-Roman, Guido Tricot, Frits Van Rhee, Ronald Walker, Maurizio Zangari, John Crowley, Bart Barlogie, John D. Shaughnessy

Research output: Contribution to journalArticle

700 Scopus citations

Abstract

To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF- and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature.

Original languageEnglish (US)
Pages (from-to)2020-2028
Number of pages9
JournalBlood
Volume108
Issue number6
DOIs
StatePublished - Sep 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Zhan, F., Huang, Y., Colla, S., Stewart, J. P., Hanamura, I., Gupta, S., Epstein, J., Yaccoby, S., Sawyer, J., Burington, B., Anaissie, E., Hollmig, K., Pineda-Roman, M., Tricot, G., Van Rhee, F., Walker, R., Zangari, M., Crowley, J., Barlogie, B., & Shaughnessy, J. D. (2006). The molecular classification of multiple myeloma. Blood, 108(6), 2020-2028. https://doi.org/10.1182/blood-2005-11-013458