|
| Status |
Public on Feb 27, 2012 |
| Title |
An East-Asian polymorphism underlies BCR-ABL mutation-independent resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by high throughput sequencing
|
| Summary |
We used massively parallel DNA sequencing of paired-end ditags (DNA-PET) to identify structural genetic factors associated with disease progression and drug-resistance in representative samples from four CML patients and one CML cell line. The functional consequences of our genetic findings were evaluated in primary CML cells and cell lines, and validated in a larger CML cohort. We discovered a novel intronic deletion that correlated with imatinib-resistance, and was subsequently confirmed to be a polymorphism in normal East-Asian, but not African or Caucasian, populations. We found that the polymorphism favored expression of transcripts lacking a pro-apoptotic domain, which is critical for imatinib-induced cell death. A CML cell line containing the polymorphism also exhibited BCR-ABL-independent imatinib-resistance.
|
| |
|
| Overall design |
Structural variations of 5 human CML samples were identified by long span paired-end sequencing
|
| |
|
| Contributor(s) |
Ruan Y, Hillmer A |
| Citation(s) |
22426421 |
| |
| Submission date |
Mar 31, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Axel HILLMER |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Cologne
|
| Department |
Institute of Pathology
|
| Street address |
Kerpener Str. 62
|
| City |
Cologne |
| ZIP/Postal code |
50937 |
| Country |
Germany |
| |
|
| Platforms (2) |
| GPL9138 |
AB SOLiD System 2.0 (Homo sapiens) |
| GPL9442 |
AB SOLiD System 3.0 (Homo sapiens) |
|
| Samples (6)
|
| GSM700323 |
Genomic DNA of patient P440 blood [SOLiD v2] |
| GSM700324 |
Genomic DNA of patient P440 blood [SOLiD v3+] |
| GSM700325 |
Genomic DNA of patient P022 blood |
|
| Relations |
| SRA |
SRP006673 |
| BioProject |
PRJNA139493 |
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