E-GEOD-635 - Transcription profiling of human drug sensitive and resistant ALL cells obtained at diagnosis from 174 patients
Released on 15 June 2008, last updated on 27 March 2012
Cellular drug resistance is associated with an unfavorable prognosis in pediatric acute lymphoblastic leukemia (ALL). To identify genes conferring resistance to antileukemic agents, we analyzed the expression of >12,700 genes in sensitive and resistant ALL cells obtained at diagnosis from 174 patients. This revealed 42, 59, 54 and 22 genes (P≤0.001) that were differentially expressed in B-lineage ALL that was sensitive versus resistant to prednisolone, vincristine, asparaginase or daunorubicin, respectively, with prediction accuracies of 71-76%. Notably, 149 of the discriminating genes have not been previously associated with resistance to these anticancer agents. These included carbohydrate-metabolism and transcription-associated genes for prednisolone, cytoskeleton and extracellular matrix genes for vincristine, ribosomal protein and translation-associated genes for asparaginase, and RAS signaling and nucleosome remodeling complex genes for daunorubicin. The identification of novel genomic determinants of cellular drug resistance provides new insights for overcoming drug resistance in acute lymphoblastic leukemia.
transcription profiling by array, unknown experiment type
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. Amy Holleman, Meyling H Cheok, Monique L den Boer, Wenjian Yang, Anjo J P Veerman, Karin M Kazemier, Deqing Pei, Cheng Cheng, Ching-Hon Pui, Mary V Relling, Gritta E Janka-Schaub, Rob Pieters, William E Evans. N Engl J Med 351(6):533-42 (2004)