High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone

Br J Haematol. 2013 Jun;161(5):695-700. doi: 10.1111/bjh.12338. Epub 2013 Apr 9.

Abstract

Cereblon (CRBN) has recently been identified as a target for immunomodulatory drugs (IMiDs) and its downregulation has been linked to resistance to lenalidomide. Here, we studied CRBN expression by real time polymerase chain reaction in 49 bone marrow samples of newly diagnosed patients with multiple myeloma treated with lenalidomide and dexamethasone. Median CRBN expression was 3·45 in patients who achieved complete response, and 3·75, 2·01, 0·78, and 0·70 in those with very good partial response, partial response, stable disease and progressive disease respectively. CRBN expression levels correlated significantly with response to lenalidomide treatment (r = 0·48; P < 0·001). Among established prognostic parameters, only beta-2-microglobulin correlated with cereblon (r = 0·66; P < 0·001). A close association of CRBN with interferon regulatory factor 4 (IRF4) (P < 0·001) and with CTNNB1 (P < 0·001) was found. Overall, a statistically significant association between baseline CRBN expression and response in MM patients treated with lenalidomide is shown. CRBN expression is closely associated with IRF4, which is an important target of IMiD therapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis*
  • Bone Marrow / metabolism
  • Dexamethasone / administration & dosage
  • Humans
  • Interferon Regulatory Factors / biosynthesis
  • Lenalidomide
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism*
  • Neoplasm Proteins / biosynthesis
  • Peptide Hydrolases / biosynthesis*
  • Plasma Cells / metabolism
  • Prognosis
  • Real-Time Polymerase Chain Reaction / methods
  • Retrospective Studies
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligases
  • beta Catenin / biosynthesis

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CRBN protein, human
  • CTNNB1 protein, human
  • Interferon Regulatory Factors
  • Neoplasm Proteins
  • beta Catenin
  • interferon regulatory factor-4
  • Thalidomide
  • Dexamethasone
  • Ubiquitin-Protein Ligases
  • Peptide Hydrolases
  • Lenalidomide