Impact of genes highly correlated with MMSET myeloma on the survival of non-MMSET myeloma patients

S. Peter Wu, Ruth M. Pfeiffer, Inhye E. Ahn, Sham Mailankody, Pieter Sonneveld, Mark Van Duin, Nikhil C. Munshi, Brian A. Walker, Gareth Morgan, Ola Landgren

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Purpose: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined. Experimental Design: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients. Results: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways. Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype.

Original languageEnglish (US)
Pages (from-to)4039-4044
Number of pages6
JournalClinical Cancer Research
Volume22
Issue number16
DOIs
StatePublished - Aug 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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