The hENT1 and DCK genes underlie the decitabine response in patients with myelodysplastic syndrome

Leuk Res. 2015 Feb;39(2):216-20. doi: 10.1016/j.leukres.2014.08.016. Epub 2014 Sep 1.

Abstract

Decitabine is approved for the treatment of MDS, but resistance to this agent is common. To determine the mechanisms underlying decitabine resistance, we measured the mRNA expression of metabolism (hENT1, DCK, CDA) and apoptosis (BCL2L10) genes and found that the hENT1 mRNA level was significantly higher in response compared with non-response patients (P=0.004). Furthermore, the DCK level was significantly reduced for relapse (P=0.012) compared with those with continued marrow CR (P=0.222). These findings indicate that the decitabine metabolic pathway affects its therapeutic effects, lower hENT1 expression may induce primary resistance and down-regulated DCK expression may be related to secondary resistance.

Keywords: DCK gene; Decitabine; Resistance; hENT1 gene.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Azacitidine / administration & dosage
  • Azacitidine / analogs & derivatives*
  • Decitabine
  • Deoxycytidine Kinase / biosynthesis*
  • Down-Regulation / drug effects
  • Drug Resistance*
  • Enzyme Inhibitors / administration & dosage*
  • Equilibrative Nucleoside Transporter 1 / biosynthesis*
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes* / drug therapy
  • Myelodysplastic Syndromes* / metabolism
  • Myelodysplastic Syndromes* / pathology
  • RNA, Messenger / biosynthesis

Substances

  • Enzyme Inhibitors
  • Equilibrative Nucleoside Transporter 1
  • RNA, Messenger
  • SLC29A1 protein, human
  • Decitabine
  • Deoxycytidine Kinase
  • Azacitidine