Page 170 - Haematologica March 2020

M. Xu et al.
A
BD
C
Figure 6. Tg(hsp70:p210BCR/ABL1) trans- genic zebrafish model responds to chemotherapy. (A and B) TKI treat- ment in zebrafish larvae. 3 dpf HS WT (left panels) and Tg(hsp70:p210BCR/ABL1) (right panels) larvae treated for 48 hours with 1‰ DMSO control, 20 μmol/L imatinib, 5 μmol/L dasatinib and 10 mmol/L bosutinib. (A) WISH of lcp1 expres- sion in the drug treated larvae at 5 dpf. n/n, number of zebrafish larvae showing representative phenotype/total number of zebrafish larvae examined. Original magnifica- tion, x200. (Bottom): statistical analy- sis. Enumeration of lcp1+ signals shown in (A). Average numbers of lcp1+ cells per larva with drug treat- ment. ANOVA; mean ± SEM; ****P<0.0001. (C) Drug screening. Upper: WISH of lcp1 expression in Tg(hsp70:p210BCR/ABL1) (right) larvae and WT controls (left) at 4 dpf after treatment (1‰ DMSO, 20 mmol/L CC-223, 2.5 mmol/L FTY720) for 24 hours. n/n, number of zebrafish lar- vae showing representative pheno- type/total number of zebrafish larvae examined. Original magnification, x200. Under: Statistical analysis. 3 dpf HS WT and Tg(hsp70:p210BCR/ABL1) larvae (n=25 and n=20, n=23 and n=25, n=20 and n=15, n=22 and n=24, n=20 and n=21, n=14 and n=24, n=19 and n=19, n=20 and n=19, n=19 and n=18, n=23 and n=24, n=23 and n=17, n=16 and n=15, respectively) were treated for 24 hours with drugs (1‰ DMSO, 2.5 mmol/L FTY720, 20 mmol/L CC-223, 0.5 mmol/L BEZ235, 40 mmol/L icar- itin, 20 mmol/L AZD3759, 80 mmol/L icotinib, 40 mmol/L DB07268, 80 mmol/L NQDI-1, 40 mmol/L selonsert- ib, 20 mmol/L LY364947, 1 mmol/L ciliobrevin A, respectively). Average numbers of lcp1+ cells per larva with drug treatment. ANOVA; mean ± SEM; **P<0.01; ***P<0.001; ****P< 0.0001. (D) Sketch map of inhibitors target BCR/ABL1 kinase-dependent or kinase-independent pathways. JNK: the c-Jun N-terminal kinase. ASK: apoptosis signal-regulating kinase. TGF-β, the transforming growth factor β. EGFR: the epidermal growth factor receptor.
684
haematologica | 2020; 105(3)