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Letter
Nature Genetics  34, 85 - 90 (2003)
Published online: 21 April 2003; | doi:10.1038/ng1151


There is an Erratum (June 2003) associated with this Letter.

Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells

Meyling H. Cheok1, 2, Wenjian Yang1, Ching-Hon Pui3, 4, James R. Downing5, Cheng Cheng6, Clayton W. Naeve7, Mary V. Relling1, 4 & William E. Evans1, 4

1  The Hematological Malignancies Program: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, Tennessee 38105 USA

2  The University of Bonn, Germany

3  Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

4  The University of Tennessee, Memphis, USA

5  Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

6  Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

7  The Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Correspondence should be addressed to William E. Evans william.evans@stjude.org
To elucidate the genomics of cellular responses to cancer treatment, we analyzed the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination. Based on changes in gene expression, we identified 124 genes that accurately discriminated among the four treatments. Discriminating genes included those involved in apoptosis, mismatch repair, cell cycle control and stress response. Only 14% of genes that changed when these medications were given as single agents also changed when they were given together. These data indicate that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment, that changes in gene expression are treatment-specific and that gene expression can illuminate differences in cellular response to drug combinations versus single agents.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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