Journal Article

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

Cheng, Cheng, Evans, William E., Naeve, Clayton W., Relling, Mary V., Downing, James R., Yang, Wenjian, Cheok, Meyling H., Pui, Ching-Hon

2003

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Antineoplastic Agents - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Apoptosis / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Care and treatment / Cell cycle / Chemotherapy / Classical genetics, quantitative genetics, hybrids / Discriminant analysis / Drug dosages / Drug Resistance, Neoplasm - genetics / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression - drug effects / Gene Expression Profiling / Gene Function / General pharmacology / Genes. Genome / Genetics of eukaryotes. Biological and molecular evolution / Genomics / Health aspects / Human / Human Genetics / Humans / letter / Leukemia / Medical prognosis / Medical sciences / Mercaptopurine - administration & dosage / Mercaptopurine - therapeutic use / Metabolism / Methotrexate - administration & dosage / Methotrexate - therapeutic use / Molecular and cellular biology / Molecular genetics / Oligonucleotide Array Sequence Analysis / Ontology / Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions / Pharmacology. Drug treatments / Physiological aspects / Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy / Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics / Risk factors / Signal transduction / Tumor Cells, Cultured