XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments.

T. Bagratuni, P. Wu, D. Gonzalez de Castro, E.L. Davenport, N.J. Dickens, B.A. Walker, K. Boyd, D.C. Johnson, W. Gregory, G.J. Morgan, F.E. Davies

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding. Recent studies have highlighted the importance of IRE1alpha and X box binding protein 1 (XBP1), key members of this pathway, in normal B-plasma cell development. We have determined the gene expression levels of IRE1alpha, XBP1, XBP1UNSPLICED (XBP1u), and XBP1SPLICED (XBP1s) in a series of patients with myeloma and correlated findings with clinical outcome. We show that IRE1alpha and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival. XBP1s is an independent prognostic marker and can be used with beta2 microglobulin and t(4;14) to identify a group of patients with a poor outcome. Furthermore, we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios. This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response.
Original languageEnglish
Pages (from-to)250-253
Number of pages4
JournalBlood
Volume116
Issue number2
DOIs
Publication statusPublished - 15 Jul 2010

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers, Tumor
  • Cyclophosphamide
  • DNA-Binding Proteins
  • Dexamethasone
  • Disease-Free Survival
  • Doxorubicin
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan
  • Middle Aged
  • Multiple Myeloma
  • Prednisone
  • Prognosis
  • Proportional Hazards Models
  • Thalidomide
  • Transcription Factors
  • Vincristine

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