Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients

Haematologica. 2011 Mar;96(3):468-71. doi: 10.3324/haematol.2010.033845. Epub 2010 Dec 15.

Abstract

Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher in monoclonal gammopathy of undetermined significance than in smoldering myelomas and symptomatic myeloma (mean ± SD, 0.84 ± 0.36 vs. 0.60 ± 0.23 and 0.62 ± 0.51; P<0.01). Moreover, the median progression-free survival was significantly longer in symptomatic myeloma patients with high expression of Dicer (not reached vs. 23.6 months; P=0.02). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of monoclonal gammopathies.

Trial registration: ClinicalTrials.gov NCT00443235 NCT00461747.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / analysis
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Disease-Free Survival
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use
  • MicroRNAs / analysis
  • Middle Aged
  • Monoclonal Gammopathy of Undetermined Significance / genetics*
  • Monoclonal Gammopathy of Undetermined Significance / mortality
  • Monoclonal Gammopathy of Undetermined Significance / pathology
  • Monoclonal Gammopathy of Undetermined Significance / therapy
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Prognosis
  • Ribonuclease III / genetics*
  • Ribonuclease III / metabolism
  • Spain
  • Up-Regulation

Substances

  • Biomarkers
  • MicroRNAs
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • Melphalan

Associated data

  • ClinicalTrials.gov/NCT00443235
  • ClinicalTrials.gov/NCT00461747