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.

Loss of HOXA10 causes endometrial hyperplasia progressing to endometrial cancer

“…These observations confirm that chronic loss of HOXA10 promotes the development of low-grade, well-differentiated endometrioid carcinoma in situ. Misexpression of HOX genes including HOXA10 is reported in esophageal squamous cell carcinoma, breast cancer, neuroblastoma, lung cancer, melanoma, bone cancer, blood cancer, colorectal cancer, prostate, ovarian, and cervical cancers (Hajirnis & Mishra 2021;Ponrathnam et al 2021). Interestingly, forced expression of HOXA10 causes endometrioid-like differentiation of mouse ovarian surface epithelium, and overexpression of HOXA10 is seen in ovarian endometrioid adenocarcinoma (Cheng et al 2005;Tanwar et al 2013).…”

Loss of HOXA10 causes endometrial hyperplasia progressing to endometrial cancer

“…These observations confirm that chronic loss of HOXA10 promotes the development of low-grade, well-differentiated endometrioid carcinoma in situ. Misexpression of HOX genes including HOXA10 is reported in esophageal squamous cell carcinoma, breast cancer, neuroblastoma, lung cancer, melanoma, bone cancer, blood cancer, colorectal cancer, prostate, ovarian, and cervical cancers (Hajirnis & Mishra 2021; Ponrathnam et al . 2021).…”

Haemocyte‐mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites

“…Also, overproliferation and differentiation of haemocytes following parasitization were observed [109]. Mutations in different genes in these pathways lead to over proliferation of lamellocytes and the development of tumor [112]. The lesswright mutation leads to activation of the Dorsal and Dif proteins that are key transcription factors in haematopoiesis; Dorsal primarily stimulates plasmatocyte production while Dif controls both plasmatocyte and lamellocyte production [113].…”