Clinical and biological implications of MYC activation: A common difference between MGUS and newly diagnosed multiple myeloma

W. J. Chng, G. F. Huang, T. H. Chung, S. B. Ng, N. Gonzalez-Paz, T. Troska-Price, G. Mulligan, M. Chesi, P. L. Bergsagel, R. Fonseca

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed gene expression data sets generated on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes overexpressed in MM were enriched for cell cycle, proliferation and MYC activation gene sets. Upon dissecting the relationship between MYC and cell-cycle gene sets, we identified and validated an MYC activation signature dissociated from proliferation. Applying this signature, MYC is activated in 67% of myeloma, but not in MGUS. This was further confirmed by immunohistochemistry (IHC) using membrane CD138 and nuclear MYC double staining. We also showed that almost all tumors with RAS mutations expressed the MYC activation signature, and multiple mechanisms may be involved in activating MYC. MYC activation, whether assessed by gene-expression signature or IHC, is associated with hyperdiploid MM and shorter survival even in tumors that are not proliferative. Bortezomib treatment is able to overcome the survival disadvantage in patients with MYC activation.

Original languageEnglish (US)
Pages (from-to)1026-1035
Number of pages10
JournalLeukemia
Volume25
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • MGUS
  • MYC
  • bortezomib
  • hyperdiploid
  • myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Clinical and biological implications of MYC activation: A common difference between MGUS and newly diagnosed multiple myeloma'. Together they form a unique fingerprint.

  • Cite this