Drosophila Hox genes induce melanised pseudo-tumours when misexpressed in hemocytes

Abstract

Homeotic genes are the key early determinants of cell identity along the anterior-posterior body axis across bilaterians. More recently, however, several late non-homeotic functions of hox genes have emerged in a variety of organogenesis processes, including in mammals. Being crucial factors in determining cell identity and organogenesis, the misregulation of hox genes is likely to be associated with defects in these processes. Several studies have reported misexpression of hox genes in a variety of malignancies including acute myeloid leukaemia. Considering that Drosophila is a well-established model for the study of haematopoiesis, we ectopically expressed the hox genes, Dfd, Ubx, abd-A and Abd-B, to ask if and how it will alter the process of haematopoiesis. We observed black melanised spots circulating in the viscera of the larvae and extensive lethality at during the pupal stage in these conditions. Such abnormalities are the hallmark of dysregulated haematopoiesis. We also observed an increase in blood cell number as well as their enhanced differentiation into lamellocytes. Our study opens a new possibility of addressing the function hox genes in normal and leukemogenic hematopoiesis with potential implications in downstream targets for diagnostic markers and therapy.\n\nSummaryDrosophila Hox genes, when expressed in blood cells, are leukemogenic, induce cell autonomous proliferation and differentiation. This reinforces previous studies in vertebrates and allows for Hox induced leukaemia to be studied in Drosophila.