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.
Footnotes
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L.P.J. received a post-doctoral grant from Ligue Contre le Cancer-Comitédu Rhône, and T.N.-D. received a PhD grant from Fondation de France. Work in our laboratories was partially funded by Oddrun Mjålands Stiftelse for Kreftforskning and Medeco's Stiftelse.
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Parts of this work were previously presented as a poster as follows: Jordheim LP, Nguyen T, Thomas X, Dumontet C, and Tavtigian SV (2007) Differential allelic expression in genes involved in the cellular response to the nucleoside analogue cytarabine. Gordon Research Conference on Nucleosides, Nucleotides & Oligonucleotides; 2007 July 1–6; Newport, RI. Gordon Research Conferences, West Kingston, RI.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.108.023184.
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ABBREVIATIONS: AML, acute myeloid leukemia; DAE, differential allelic expression; cSNP, exonic single nucleotide polymorphism; rSNP, regulatory SNP; PCR, polymerase chain reaction; gDNA, genomic DNA; RT, reverse transcription.
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The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material. - Received July 18, 2008.
- Accepted September 4, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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Differential Allelic Expression in Leukoblast from Patients with Acute Myeloid Leukemia Suggests Genetic Regulation of CDA, DCK, NT5C2, NT5C3, and TP53
