Group Accession SAMEG47323

Submission Title:An East-Asian polymorphism underlies BCR-ABL mutation-independent resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia
Submission Identifier:GEN-SRP006673
Submission Description: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
Submission Release Date:2014-12-06
Submission Update Date:2015-04-02
Submission Reference Layer:false
Databases:ENA Sample Group Service Link  SRP006673

Name: GEO; Address: ; Role: Submitter; Email: ; URI:
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Samples in group:6
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