Impact of global and gene-specific DNA methylation pattern in relapsed multiple myeloma patients treated with bortezomib

Leuk Res. 2013 Jun;37(6):641-6. doi: 10.1016/j.leukres.2013.01.013. Epub 2013 Feb 8.

Abstract

We studied seventy-five patients with relapsed MM treated with bortezomib-based regimens. DNA was isolated from bone marrow samples at the time of relapse. Global methylation was determined by ELISA, and CpG island DNA methylation profile of 30 genes by a DNA methylation PCR system. Patients with more than 3.95% of total DNA methylated achieved better overall survival (OS) (p=0.004). A relatively low methylation percentage (<1.07%) of NFKB1 was also associated with longer OS after bortezomib treatment (p=0.015). The combination of highly methylated global genome with low NFKB1 methylation status defined a specific subset of patients with better prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • DNA Methylation* / physiology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Genes, Neoplasm*
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Pyrazines / therapeutic use*
  • Recurrence
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib