E-GEOD-7114 - Transcription profiling of a human chronic myelogenous leukemia cell line resistant to cyclophosphamide

Released on 25 April 2009, last updated on 5 October 2015
Homo sapiens
Samples (10)
Array (1)
Protocols (4)
Acquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000 fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors. Experiment Overall Design: A CML cell line and a CP resistant subline were compared by gene array. In addition other markers, the expression of BCR-ABL and the sensitivity to tyrosine kinase inhibitors were tested.
Experiment types
transcription profiling by array, cell type comparison
Investigation descriptionE-GEOD-7114.idf.txt
Sample and data relationshipE-GEOD-7114.sdrf.txt
Raw data (1)E-GEOD-7114.raw.1.zip
Processed data (1)E-GEOD-7114.processed.1.zip
Array designA-AFFY-1.adf.txt