Drosophila Hox genes induce melanized pseudo-tumors when misexpressed in hemocytes

Abstract

AbstractHox genes are early determinants of cell identity along the anterior–posterior body axis across bilaterians. Several late non-homeotic functions of Hox genes have emerged in a variety of processes involved in organogenesis in several organisms, including mammals. Several studies have reported the misexpression of Hox genes in a variety of malignancies including acute myeloid leukemia. The Hox genesDfd, Ubx, abd-AandAbd-Bwere overexpressed via the UAS-Gal4 system usingCg-Gal4, Lsp2-Gal4, He-Gal4andHmlD3-Gal4as specific drivers. Genetic interaction was tested by bringing overexpression lines in heterozygous mutant backgrounds of Polycomb and trithorax group factors. Larvae were visually scored for melanized bodies. Circulating hemocytes were quantified and tested for differentiation. Pupal lethality was assessed. Expression ofDfd, Ubxandabd-A,but notAbd-Bin the hematopoietic compartment ofDrosophilaled to the appearance of circulating melanized bodies, an increase in cell number, cell-autonomous proliferation, and differentiation of hemocytes. Pupal lethality and melanized pseudo-tumors were suppressed inPsc1andesc2backgrounds while polycomb group member mutationsPc1andSu(z)123and trithorax group member mutationTrlR85enhanced the phenotype.Dfd, Ubxandabd-Aare leukemogenic. Mutations in Polycomb and trithorax group members modulate the leukemogenic phenotype. Our RNAseq ofCg-Gal4 > UAS-abd-Ahemocytes may contain genes important to Hox gene induced leukemias.