Differential allelic expression in leukoblast from patients with acute myeloid leukemia suggests genetic regulation of CDA, DCK, NT5C2, NT5C3, and TP53

Drug Metab Dispos. 2008 Dec;36(12):2419-23. doi: 10.1124/dmd.108.023184. Epub 2008 Sep 5.

Abstract

mRNA expression levels of certain genes have shown predictive value for the outcome of cytarabine-treated AML-patients. We hypothesized that genetic variants play a role in the regulation of the transcription of these genes. We studied leukoblasts from 82 patients with acute myeloid leukemia and observed various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes. Our attempts to identify the causative regulatory single nucleotide polymorphisms by a bioinformatics approach did not succeed. However, our results indicate that genetic variations are at least in part responsible for the differences in overall expression levels of these genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics*
  • Alleles*
  • Cytarabine / therapeutic use
  • Cytidine Deaminase / genetics*
  • Deoxycytidine Kinase / genetics*
  • Equilibrative Nucleoside Transporter 1 / genetics
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glycoproteins / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Equilibrative Nucleoside Transporter 1
  • Glycoproteins
  • SLC29A1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cytarabine
  • Deoxycytidine Kinase
  • 5'-Nucleotidase
  • NT5C2 protein, human
  • NT5C3A protein, human
  • Cytidine Deaminase