Fig. 4.

Effects of TKi on CML cells endowed with ALDH activity. a K562 and LAMA-84 cells (3 × 10⁵/mL) were treated with DMSO (vehicle), 1 μM imatinib or 4 nM ponatinib at time 0 and incubated for 72 h. The enzymatic activity of ALDH in viable cells was assessed by flow cytometry. The gating for ALDH activity-negative cells (control) was performed in the presence of the ALDH inhibitor DEAB (upper plots). Percentages of ALDH activity-positive viable cells averages (± SD) from three independent experiments are show in representative plots. b Data from a are plotted in the graphs together with statistical analysis; *p < 0.05, **p < 0.01; ns not significant. Data obtained from similar experiments carried out with LAMA-84R are also shown. See Supplementary Fig. S2c for representative dot plots from one out of three experiments performed with LAMA-84R (electronic supplementary material). c Patient-derived CML cells (3 × 10⁵/mL) were treated with DMSO (vehicle), 1 μM imatinib, 4 nM ponatinib, or 10 μM XMD8-92 at time 0 and incubated for 72 h. The percentages of ALDH activity-positive viable cells from three patients (mean ± SD) were determined by flow cytometry. *p < 0.05, **p < 0.01, ***p < 0.001. Data obtained for individual patients are shown in Supplementary Fig. S2d (see electronic supplementary material). ALDH aldehyde-dehydrogenase, CML chronic myeloid leukemia, DMSO dimethyl-sulfoxide, TKi tyrosine kinase inhibitors