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A CML Drosophila model for treatment screening
Discussion
In this study, we established a transgenic Drosophila model expressing human BCR-ABL1 to serve as a credible platform for CML drug screening. Contrary to what has been done previously by Fogerty et al. where chimeric human/fly BCR-ABL1 was expressed in Drosophila33 we expressed a full human BCR-ABL1p210 protein. In a recent
study, a CML Drosophila model expressing the human BCR-ABL1p210 was used to study genes and pathways that play a role in CML onset and progression.34
The Drosophila eye, with its highly organized reiterative ommatidial structure, constitutes an efficient and relative- ly easy read out capable of amplifying subtle changes caused by disturbance to normal development. Therefore, we chose this epithelial monolayer as a target tissue for
Figure 2. Rough eye phenotype induced by overexpression of human BCR-ABL1p210/T315I. Light (A-D, M-N) and scanning electron (E-L, O-R) micrographs of adult Drosophila melanogaster compound eyes expressing BCR-ABL1P210/T315I under the control of the eye specific promoter GMR-GAL4. Flies were raised on 18oC, 25oC or 29oC. I-L and Q-R are high magnifications of the centremost region of E-H and O-P respectively (1,370x). GMR-GAL4>w1118 were used as control. Ommatidial facets are depicted in (I) by (*), misplaced 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 represents mean ± SEM. ****, P<0.0001.
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