Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution

ABSTRACT: 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-A

ORGANISM(S): Mus musculus

SUBMITTER: Boyang Zhao 

PROVIDER: E-GEOD-72910 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress