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. 2021 Jan 1;11(6):2691–2705. doi: 10.7150/thno.50571

Figure 6.

Figure 6

NGF protects CML cells against imatinib through KDM6A-mediated activation of TRKA. (A) Cell survival comparisons between K562 (Ctrl), KDM6A KO and KDM6A KO cells rescued by either WT or ED KDM6A constructs after 3 days of growth in 10% FBS containing medium supplemented with or without NGF (100 ng/mL) in the presence of 0.5 μM imatinib. Live cells were counted by Trypan blue exclusion and results calculated as a percentage of growth seen with untreated controls. Mean ± s.d. are given for three independent experiments. Unpaired, two-tailed Student's t-test; ***p < 0.001; n.s., not significant. (B) Ectopic Flag-TRKA expression in K562 KDM6A KO cells increased NGF-induced cell survival after 24 h treatment with 0.5 μM imatinib. Apoptosis was determined by FACS. Mean ± s.d. are given for three independent experiments. Unpaired, two-tailed Student's t-test; *p < 0.05. One-way ANOVA; ***p < 0.001. (C-E) Western blotting analyses comparing AKT and ERK signaling responses elicted by 100 ng/mL NGF and/or 1 h pretreatment with 10 μM imatinib. K562 control versus KDM6A KO K562 cells (C), KDM6A KO K562 cells after reconstitution with KDM6A WT or KDM6A-ED (D) and parental MEG-01 CML versus KDM6A knock down cells (E). (F) A schematic showing KDM6A mediated signaling responses directing imatinib resistance in CML.