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. 2021 Aug 20;11:686765. doi: 10.3389/fonc.2021.686765

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Copyright © 2021 Lu, Han, Busquets, Collins, Lodi, Marszalek, Konopleva and Tiziani

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The synergy between IACS-0101759 and AC220 was validated using ATP bioluminescence assay combined with the Bliss independence model, viable cell counting, and apoptosis assay at serial doses. (A) Bliss index (based on Bliss independence model) for 13 FLT3 inhibitors administered in 3 leukemia cell lines (U937, OCI-AML2 and OCI-AML3) at 9 different doses (0.0000128:5x:5 µM) in combination with 10 nM IACS-010759. Bliss index values higher than 0.1 (outside of the black dashed line) represents strong synergism. (B) Number of viable cells and (C) fraction of apoptotic cells following treatment at multiple doses (0.25x, 0.5x, 1x, 2x, and 4x) of AC220 (1x: 500 nM) and/or IACS-010759 (1x: 10 nM). Error bars show standard deviations. IACS: IACS-010759.