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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2019

AutorInnen: Gleixner, KV; Sadovnik, I; Schneeweiss, M; Eisenwort, G; Byrgazov, K; Stefanzl, G; Berger, D; Herrmann, H; Hadzijusufovic, E; Lion, T; Valent, P

Titel: A kinase profile-adapted drug combination elicits synergistic cooperative effects on leukemic cells carrying BCR-ABL1T315I in Ph+ CML.

Quelle: Leuk Res 2019; 78: 36-44.



Autor/innen der Vetmeduni Vienna:

Hadzijusufovic Emir

Beteiligte Vetmed-Organisationseinheiten
Klinische Abteilung für Interne Medizin Kleintiere


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 lines (K562, K562R, KU812, KCL22) and Ba/F3 cells harboring various BCR-ABL1 mutant-forms. We found that bosutinib synergizes with dasatinib in inducing growth inhibition and apoptosis in all CML cell lines and in Ba/F3 cells exhibiting BCR-ABL1


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