Validation of a Drosophila model of wild type and T315I mutated BCR-ABL1 in chronic myeloid leukemia: An effective platform for treatment screening.

In this study, we expressed human BCR-ABL1p210 and the resistant BCR-ABL1p210/T315I fusion oncogenes in Drosophila eyes. Expression of BCR-ABL1p210/T315I resulted in severe distortion of the ommatidial architecture of adult eyes and with more prominent rough eye phenotype compared to milder phenotypes in BCR-ABL1p210 reflecting a stronger oncogenic potential of the mutant. We then assessed the efficacy of the currently used tyrosine kinase inhibitors in BCR-ABL1p210 and BCR-ABL1p210/T315I expressing flies. Treatment of BCR-ABL1p210 expressing flies with potent kinase inhibitors (dasatinib and ponatinib) resulted in the rescue of ommatidial loss and restoration of normal development. Taken together, we provide chronic myeloid leukemia tailored BCR-ABL1p210 and BCR-ABL1p210/T315I fly model which can be used to test new compounds with improved therapeutic indices. PMID: 31101753 [PubMed - as supplied by publisher]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research