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Drug Metabolism and Disposition Fast Forward
First published on September 5, 2008; DOI: 10.1124/dmd.108.023184

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Received for publication July 18, 2008.
Revised August 20, 2008.
Accepted for publication September 4, 2008.

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

Lars Petter Jordheim 1*, Tu Nguyen-Dumont 2, Xavier Thomas 3, Charles Dumontet 1, Sean V Tavtigian 2

1 INSERM U590 2 International Agency of Research on Cancer 3 Hopital Edouard Herriot

* Address correspondence to: E-mail: jordheim{at}yahoo.com

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 leucoblasts from 82 AML patients and observed various extent and frequency of differential allelic expression in CDA, DCK, NT5C2, NT5C3 and TP53 genes. Our attempts to identify the causative regulatory SNPs 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.


Key words: gene regulation, genetic polymorphism, pharmacogenetics, polymorphisms




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