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A. Al Outa et al.
resistance to imatinib, nilotinib and dasatinib in CML patients and this was confirmed in our model whereby the characteristic posterior eye defect did not show ommatidial rescue when feeding BCR-ABL1p210/T315I expressing flies imatinib (Figure 4 Q, W, R, X), dasatinib (Figure 5 L, P) or nilotinib (Online Supplementary Figure S1
Q, W, R, X). However, feeding ponatinib to BCR- ABL1p210/T315I expressing flies did not show the expected rescue of the posterior eye defect (Figure 6 L, P). Western blot analysis confirmed the expression and phosphoryla- tion of BCR-ABL1p210 and BCR-ABL1p210/T315I in Drosophila eyes from untreated or treated flies (Figures 5-6).
Figure 1. Rough eye phenotype induced by over- expression of human BCR-ABL1p210. Light (A-D, M- N) and scanning electron (E-L, O-R) micrographs of adult Drosophila compound eyes expressing BCR-ABL1p210 under the control of the eye specific promoter GMR-GAL4. Flies were raised on 18°C (A, B, E, F, I, J) 25oC (C, D, G, H, K, L) or 29oC (M- R). I-L and Q-R are high magnifications of the cen- tremost region of E-H and O-P respectively (1,370x). GMR-GAL4>w1118 were used as control. Ommatidial facets are depicted in (I) by (*), mis- placed mechanosensory bristles in (J) depicted by arrowheads and ommatidial fusions in (Q) are shown by arrow. Posterior is to the left. Lower right panel represents quantification of severity of roughness of the adult fly eye using a grading scale. Genotypes indicated are under the control of eye specific promoter GMR-GAL4. Data repre- sents mean ± SEM. ****, P<0.0001.
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haematologica | 2020; 105(2)