A kinase profile-adapted drug combination elicits synergistic cooperative effects on leukemic cells carrying BCR-ABL1^T315I in Ph+ CML.

ABSTRACT: In chronic myeloid leukemia (CML), resistance against second-generation tyrosine kinase inhibitors (TKI) remains a serious clinical challenge, especially in the context of multi-resistant BCR-ABL1 mutants, such as T315I. Treatment with ponatinib may suppress most of these mutants, including T315I, but is also associated with a high risk of clinically relevant side effects. We screened for alternative treatment options employing available tyrosine kinase inhibitors (TKI) in combination. Dasatinib and bosutinib are two second-generation TKI that bind to different, albeit partially overlapping, spectra of kinase targets in CML cells. This observation prompted us to explore anti-leukemic effects of the combination dasatinib + bosutinib in highly resistant primary CML cells, various CML cell li

SUBMITTER: Gleixner KV 

PROVIDER: S-EPMC6834439 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature