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

Abstract

Hox 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 genes Dfd, Ubx, abd-A and Abd-B were overexpressed via the UAS-Gal4 system using Cg-Gal4, Lsp2-Gal4, He-Gal4 and HmlD3-Gal4 as 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 of Dfd, Ubx and abd-A, but not Abd-B in the hematopoietic compartment of Drosophila led 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 in Psc1 and esc2 backgrounds while polycomb group member mutations Pc1 and Su(z)123 and trithorax group member mutation TrlR85 enhanced the phenotype. Dfd, Ubx and abd-A are leukemogenic. Mutations in Polycomb and trithorax group members modulate the leukemogenic phenotype. Our RNAseq of Cg-Gal4 > UAS-abd-A hemocytes may contain genes important to Hox gene induced leukemias.