Efficacy of the BH3-mimetic ABT-199 in acute lymphoblastic leukemia
R Hörl, F Seyfried, S Demir, J Zinngrebe, S Köhrer, KM Debatin, LH Meyer · Klinische Pädiatrie · 2016 · Heft 05
Bibliografische Angaben
Zusammenfassung
Introduction: Acute lymphoblastic leukemia (ALL) cells can evade from apoptosis by upregulating anti-apoptotic proteins. Mcl-1 and Bcl-2 are frequently overexpressed in ALL, thus, appearing as promising targets for anti-ALL therapy. Methods: In vitro/ex vivo exposure of cell lines and primary patient-derived xenograft samples (pdx) to ABT-199, Dinaciclib and chemotherapy, assessment of cellular viability, generation of Mcl-1 knockout cell lines by CRISPR/Cas9, Western blot, NOD/SCID human ALL mouse model. Results: 4/6 cell lines and 14/16 pdx samples were highly sensitive to ABT-199. Resistance was associated wi…