Sessile hemocytes derived from embryogenesis are found clustered under the larval epidermis (Figure 1) and attached to the larval imaginal discs in an organized manner [41]

Sessile hemocytes derived from embryogenesis are found clustered under the larval epidermis (Figure 1) and attached to the larval imaginal discs in an organized manner [41]. myriad of diseases, including cancer. Several studies used the leukemic fly to understand the transformative activity and genetic interactions of human leukemic proteins while creating a potential platform for deciphering new therapeutic targets. Hematological diseases, including leukemia or blood cancer are the result of derangements in the normal hematopoietic process. Hematopoiesis is the process whereby self-renewing multipotent hematopoietic stem cells (HSCs) differentiate into different types of blood lineages. The myeloid lineage further differentiates into different cell types, including erythrocytes, megakaryocytes (which give rise to platelets), and macrophages. The lymphoid lineage comprises B and T lymphocytes and natural killer cells. In vertebrates, hematopoiesis occurs through the primitive and definitive waves, which are spatially and temporally distinct [1]. The primitive wave is a transient wave that supports embryonic development through the production of erythrocytes by an extraembryonic yolk sac [2]. Definitive hematopoiesis is a de novo lifelong wave that gives rise to all blood cell types in mature organisms. In mammals, HSCs originate at embryonic stage in aorta/gonad/mesonephros (AGM) region of the embryo proper and homes hematopoietic organs such as the bone marrow and fetal liver [3]. Being an ectotherm that depends on external sources of heat, harbors an open circulatory system with low hydrostatic pressure characterized by the presence of a simple tube-like heart (also termed dorsal vessel) and interstitial fluid known as hemolymph. The hemolymph is pumped from the posterior to the anterior of the fly body by the cardiac tube and it carries Ozenoxacin nutrients, metabolites, hormones, peptides, and hemocytes [4]. This review briefly introduces the hematopoietic system in and focuses on studies that used human leukemogenic proteins to demonstrate their effect on hematopoietic and Ozenoxacin non-hematopoietic fly tissues and highlights the potential role of the fly in translational leukemia research. Hematopoiesis in a Glance 2.1. Circulating Hemocytes and Their HIP Response to Oncogene Expression Major cellular immune functions in are orchestrated by three types of terminally differentiated hemocytes, namely plasmatocytes, crystal cells, and lamellocytes, which are in close resemblance to the vertebrate myeloid lineage [5] and play an important role in the cell mediated innate immunity in flies [6]. Although flies are known to rely solely on their innate immunity for combatting pathogens, immune priming was described in which allows for a specific immune response upon secondary infection, specifically with and [7]. Furthermore, Tasetto et al. suggested that a systemic RNAi-based adaptive antiviral response in is mediated by circulating immune cells [8], indicating a resemblance to mammalian adaptive immunity with albeit distinct molecular and cellular mechanisms. Further studies in the field are required to properly characterize adaptive immunity in flies. larvae hemocytes are housed in three main compartments: the hemolymph, subepithelial patches (sessile hemocytes), and in lymph gland [9]. Accounting for 90C95% of the circulating hemocytes, plasmatocytes are considered the main representative hemocytes. They are available throughout all developmental stages with a phagocytic activity towards apoptotic debris [10] and microbes [11,12], thereby resembling mammalian macrophages/monocytes [5,10,13]. Plasmatocytes are capable of secreting antimicrobial peptides (AMPs) and hence mediate humoral response [14,15]. The integration of the systemic responses and the maintenance of the organismal homeostasis necessitate the presence of a crosstalk between plasmatocytes and organs acting as barriers between the fly and its surrounding environment. Reported cross-talks include, for example, those of plasmatocytes with the gut [16] and the fat body as well as the visceral muscles [17,18,19,20]. The remaining ~5% of the circulating hemocytes are platelet-like cells known as crystal cells, which are non-phagocytic, harboring crystalline inclusions [21,22] that execute melanization responses, such as those required for wound healing [23] and innate immunity [24]. Crystal cells harbor prophenoloxidase, which is the essential enzyme required for melanin synthesis [25]. Both crystal cells and plasmatocytes play an important role during clotting response by secreting hemolectin, a Ozenoxacin protein that shares conserved domains present in human von Willebrand factor, coagulation factor V/VIII as well as complement factors [26,27,28]. The third type of hemocytes, known as lamellocytes, are cryptic, stress-induced cells that are rare in normal conditions and are induced in huge numbers for encapsulation of large foreign particles such as.