Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells
- 21 April 2003
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 34 (1) , 85-90
- https://doi.org/10.1038/ng1151
Abstract
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.Keywords
This publication has 27 references indexed in Scilit:
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociationNature, 2003
- MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemiaNature Genetics, 2001
- A gene expression database for the molecular pharmacology of cancerNature Genetics, 2000
- High density synthetic oligonucleotide arraysNature Genetics, 1999
- Drug target validation and identification of secondary drug target effects using DNA microarraysNature Medicine, 1998
- Transcripts with splicings of exons 15 and 16 of the hMLH1 gene in normal lymphocytes: implications in RNA-based mutation screening of hereditary non-polyposis colorectal cancerEuropean Journal Of Cancer, 1998
- Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiationNature, 1997
- Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.Journal of Clinical Investigation, 1996
- Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia.Journal of Clinical Investigation, 1994
- The Purine Path to ChemotherapyScience, 1989