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. 2021 Dec 15;11(12):6042–6059.

Figure 6.

Figure 6

Effects of BEZ235 and copanlisib on niche-induced TKI resistance of CML cells. KU812 cells (A) and K562 cells (B) were incubated in control medium (0) or in medium containing nilotinib (100-250 nM), ponatinib (10-25 nM), asciminib (20-50 nM), BEZ235 (3 μM) and copanlisib (3 μM) or in medium with a combination of drugs (BEZ235+nilotinib, BEZ235+ponatinib, BEZ235+asciminib, copanlisib+nilotinib, copanlisib+ponatinib, copanlisib+asciminib) in the absence or in presence (Co-culture) of CAL-72 cells at 37°C for 48 hours. Then, cells were examined by flow cytometry to determine the percentage of apoptotic (Annexin-V/DAPI-positive) cells. Results represent the mean ± SD of three independent experiments. Asterisk (*): P<0.05. Primary CML MNC (mononuclear cells) (C) were incubated in control medium (0) or in medium containing nilotinib (5 μM), ponatinib (0.5 μM), BEZ235 (5 μM) and copanlisib (5 μM) or in medium with a combination of drugs (BEZ235+nilotinib, BEZ235+ponatinib) or (copanlisib+nilotinib, copanlisib+ponatinib) in the absence or in presence (Co-culture) of CAL-72 cells at 37°C for 48 hours. Then, cells were examined by flow cytometry to determine the percentage of CD34+/CD38-/Annexin-V-positive cells among DAPI-negative cells. Results represent the mean ± SD of twelve independent experiments.