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Series GSE72910 Query DataSets for GSE72910
Status Public on Apr 05, 2016
Title Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In this study, using a murine model of Ph+ acute lymphoblastic leukemia (Ph+ ALL), a combined pharmacological profile and drug selection experimental approach identified distinct stages of tumor clonal evolution with vulnerabilities to sets of small molecules. Through genotypic, phenotypic, signaling, and binding measurements, we identified the mutation V299L in the ABL1 kinase domain as mediator for an on-target ABL1 inhibition and hence the sensitization phenotype. To further rule out any off-target effects, we performed RNA-seq analysis of select derived cell lines. Variant calls suggest that although there were other mutations, the only mutation shared among cell lines with the sensitization phenotype and that went from 0% to 100% variant allele frequency was c.895G>C, leading to BCR-ABL1 V299L. In addition, transcriptional profile does not suggest functional changes in BCR-ABL1 V299L and WT cell lines.
Overall design RNA-seq of parental murine Ph+ acute lymphoblastic leukemia (Ph+ ALL) cell line and derived cell lines (via dose escalating concentrations of dasatinib or DMSO vehicle control).
Contributor(s) Zhao B, Lauffenburger DA, Hemann MT
Citation(s) 26924578
Submission date Sep 10, 2015
Last update date May 15, 2019
Contact name Boyang Zhao
Organization name MIT
Street address 500 Main Street
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (10)
GSM1874423 ALL (DMSO 1x)
GSM1874424 ALL dasatinib IC90 1x biological replicate A
GSM1874425 ALL dasatinib IC90 1x biological replicate B
BioProject PRJNA295303
SRA SRP063569

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Supplementary file Size Download File type/resource
GSE72910_expression.merged_counts.csv.gz 475.2 Kb (ftp)(http) CSV
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Processed data are available on Series record
Raw data are available in SRA

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