LCK activation in PPR patients and efficacy of LCK inhibitors in decreasing cell viability of GC-resistant T-ALL cell lines. (A) LCK Y505 is downregulated in PPR (n = 33, mean 6346 ± 1089) in comparison with PGR (n = 54, mean 15 291 ± 2370) patients (Mann-Whitney t test, P = .001). (B) The active form of LCK, Src Y416, is upregulated in PPR (n = 33, mean 38 430 ± 6733) in comparison with PGR (n = 54, mean 21 120 ± 1623) patients (Mann-Whitney t test, P = .01). (C) Total form of LCK is not different between PPR (n = 27, mean 51 469 ± 5191) and PGR (n = 49, mean 52 463 ± 3977) patients. Results are presented as mean ± SD. (D-F) Cell viability in ALL-SIL, CCRF-CEM, and TALL-1 cells after 48 hr of treatment with dasatinib, bosutinib, nintedanib, and WH-4-023, measured by MTT assay (n = 3 for all experiments). Results are presented as means ± SEM. (G-I) WB analysis of total LCK, LCK Y505, and Src Y416 expression in ALL-SIL, CCRF-CEM, and TALL-1. Cells were treated with DMSO only (Ctrl), dasatinib, bosutinib, nintedanib, or WH-4-023 overnight at the compound concentrations corresponding to the GI₅₀ at 48 hr. Bos, bosutinib; Das, dasatinib; Nint, nintedanib; WH, WH-4-023.