Response of KCL22 and TKI-Resistant KCL22 cell-lines to Ponatinib and NVP-BEZ235

Resistance to tyrosine kinase inhibitors (TKIs), including the 3rd generation TKI ponatinib, in chronic myeloid leukaemia (CML) is a significant clinical problem. However, there is a lack of suitable cellular models to investigate the mechanism of TKI resistance in vitro.In this study, we generated KCL22 cells with acquired BCR-ABL independent resistance following culture in ponatinib. We then generated RNA sequencing (RNA-Seq) data for untreated and ponatinib treated cells. In addition, we generated RNA-Seq following mTOR inhibition using NVP-BEZ235. RNA-Seq analysis and gene ontology enrichment allowed detection of aberrant transcriptional response of ponatinib-resistant cells. This may lead to identification of novel drug targets for TKI resistant CML patients.