Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells.
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.
Cheok
Meyling H
MH
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, Tennessee 38105 USA.
Yang
Wenjian
W
Pui
Ching-Hon
CH
Downing
James R
JR
Cheng
Cheng
C
Naeve
Clayton W
CW
Relling
Mary V
MV
Evans
William E
WE
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D015122:Mercaptopurine / Q000008:administration & dosage / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015122:Mercaptopurine; D008727:Methotrexate