Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that results from a chromosomal translocation between chromosome 9 and chromosome 22. The resulting fusion gene ( BCR-ABL ) encodes a constitutively active BCR-ABL tyrosine kinase. Some mutations of this oncogene, especially the Threonine 315 to Isoleucine substitution of the ABL kinase is resistant to first and second-generation tyrosine kinase inhibitors (TKIs) conventionally used in CML therapy. We have previously validated a CML fruit fly model for drug screening using the adult fly compound eye. Here we expressed wild-type BCR-ABL P210 and mutated BCR-ABL T315I in Drosophila melanogaster hematopoietic system to understand the phenotypic consequences of this expression and its impact on innate immune pathways. Flies expressing both wild-type BCR-ABL P210 and mutant BCR-ABL T315I showed increased number of circulating hemocytes, disruption in sessile patterning of resident hemocytes, dysregulation in the humoral Toll, ImD, and JAK/STAT pathways at the mRNA level in both the 3 rd instar larva and adult stages. Of note, BCR-ABL T315I flies presented more severe phenotypes and a higher deviation in humoral dysregulation than BCR -ABL P210 flies pointing towards more complex oncogenic effect of this mutant which requires further investigation.