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An East-Asian polymorphism underlies BCR-ABL mutation-independent resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia

GSE28303 Homo sapiens Genome variation profiling by high throughput sequencing 6 samples Submitted 2012/02/27 Platform GPL9138Platform GPL9442
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.
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Direct links to NCBI, no account and no request form: the whole study as GSE28303_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA139493 and SRA study SRP006673. Searching any of these in the dataset finder brings you back here.

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