Abstract
Leukemia involves different types of blood cancers, which lead to significant mortality and morbidity. Murine models of leukemia have been instrumental in understanding the biology of the disease and identifying therapeutics. However, such models are time consuming and expensive in high throughput genetic and drug screening. Drosophila melanogaster has emerged as an invaluable in vivo model for studying different diseases, including cancer. Fruit flies possess several hematopoietic processes and compartments that are in close resemblance to their mammalian counterparts. A number of studies succeeded in characterizing the fly’s response upon the expression of human leukemogenic proteins in hematopoietic and non-hematopoietic tissues. Moreover, some of these studies showed that these models are amenable to genetic screening. However, none were reported to be tested for drug screening. In this review, we describe the Drosophila hematopoietic system, briefly focusing on leukemic diseases in which fruit flies have been used. We discuss myeloid and lymphoid leukemia fruit fly models and we further highlight their roles for future therapeutic screening. In conclusion, fruit fly leukemia models constitute an interesting area which could speed up the process of integrating new therapeutics when complemented with mammalian models.
Highlights
The fruit fly Drosophila melanogaster has been used as a research organism to model a myriad of diseases, including cancer
While this study demonstrated how a Drosophila breakpoint cluster region (BCR)-ABL1 model could be exploited for studying genetic interactions in chronic myeloid leukemia (CML); we went further to test whether the system is sensitive to pharmacologic inhibition using the eye phenotype as an efficient phenotypic read-out [99]
The fruit fly bestows at our hands several tissues that range from eyes to CNS, hemocytes and the hematopoietic niche represented by lymph gland remain the tissues of choice that can be exploited for modeling leukemia
Summary
The fruit fly Drosophila melanogaster has been used as a research organism to model a myriad of diseases, including cancer. 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. Definitive hematopoiesis is a de novo lifelong wave that gives rise to all blood cell types in mature organisms. This review briefly introduces the hematopoietic system in Drosophila melanogaster and focuses on studies that used human leukemogenic proteins to demonstrate their effect on hematopoietic and non-hematopoietic fly tissues and highlights the potential role of the fly in translational leukemia research
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