Comparative analysis of a CML cell line resistant to cyclophosphamide using oligonucleotide arrays and response to TKI
From ArrayWiki
| PubMed ID: | 17403535 |
|---|---|
| Contact: | Reinhold Munker
|
| Species: | |
| Platform: | |
| Number of Samples: | 10 |
| Date Range: | 01/13/2005 - 02/02/2005 |
| Experiment Quality: | 86.14 2.36 % 91.89 |
| Link to Repository: | GSE7114 |
| Original Intensity Data: | Download |
| Clean Intensity Data: | Download |
| Original PLIER Data: | Download |
| Clean PLIER Data: | Download |
| Clean CEL Files: | Download |
| Data Rank: | 
|
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.
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.
Type: Cell type comparison
Contents |
[edit] Contributors
- Fei Bao
- Paula Polk
- Mary L Nordberg
- Diana M Veillon
- Amanda W Sun
- Michael Deininger
- David Murray
- Borje S Andersson
- Reinhold Munker
[edit] Protocols
[edit] References
[edit] Links
GEO Accession for this experiment: GSE7114. (Public on Feb 24 2007)
PubMed abstract: 17403535
RAW data: tar file.
[edit] Analysis
 Before Normalization |
 After Normalization & Cleaning |
[edit] Samples/Quality Control
| Sample | Date Scanned | Source Link | Probe Variance Data | Artifact Mask | Quality Score |
|---|---|---|---|---|---|
| Sensitive Replicate 1 | 01/13/05 09:51:03 | GSM170886 | 
| 
| 94.4429 1.96 % 96.24 |
| Sensitive Replicate 2 | 01/13/05 10:04:29 | GSM170887 | 
| 
| 94.612 1.1 % 96.75 |
| Sensitive Replicate 3 | 01/13/05 10:13:05 | GSM170888 | 
| 
| 94.0445 1.69 % 96.18 |
| Sensitive Replicate 4 | 02/02/05 09:58:33 | GSM170889 | 
| 
| 95.0489 1.11 % 96.97 |
| Sensitive Replicate 5 | 02/02/05 09:48:53 | GSM170890 | 
| 
| 94.815 3.16 % 95.83 |
| Resistant Replicate 1 | 01/13/05 11:23:12 | GSM170891 | 
| 
| 95.2138 1.28 % 96.97 |
| Resistant Replicate 2 | 01/13/05 11:30:06 | GSM170892 | 
| 
| 94.5091 2.81 % 95.85 |
| Resistant Replicate 3 | 01/13/05 11:37:30 | GSM170893 | 
| 
| 94.7837 5.02 % 94.88 |
| Resistant Replicate 4 | 02/02/05 10:08:41 | GSM170894 | 
| 
| 95.1294 2.13 % 96.5 |
| Resistant Replicate 5 | 02/02/05 10:17:51 | GSM170895 | 
| 
| 94.9519 5.72 % 94.62 |
