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Myelopoiesis and Myeloid Leukaemogenesis in the Zebrafish

DOI: 10.1155/2012/358518

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Abstract:

Over the past ten years, studies using the zebrafish model have contributed to our understanding of vertebrate haematopoiesis, myelopoiesis, and myeloid leukaemogenesis. Novel insights into the conservation of haematopoietic lineages and improvements in our capacity to identify, isolate, and culture such haematopoietic cells continue to enhance our ability to use this simple organism to address disease biology. Coupled with the strengths of the zebrafish embryo to dissect developmental myelopoiesis and the continually expanding repertoire of models of myeloid malignancies, this versatile organism has established its niche as a valuable tool to address key questions in the field of myelopoiesis and myeloid leukaemogenesis. In this paper, we address the recent advances and future directions in the field of myelopoiesis and leukaemogenesis using the zebrafish system. 1. Introduction The zebrafish is emerging as a powerful model system in which to study haematopoiesis and leukaemogenesis. In addition to the benefits afforded by scale and simplicity of this versatile genetic model system for studying developmental aspects of haematopoiesis, the last decade has seen an explosion of molecular methods and models to facilitate studies informing on haematopoietic disease biology, particularly leukaemogenesis and cancer. At its inception as a cancer model, proliferation and angiogenesis were proposed as phenotypic attributes as readouts relevant to cancer pathogenesis [1]. However, it was the generation of a transgenic zebrafish expressing the C-myc oncogene under the control of the rag2 promoter that went on to develop T-cell acute lymphoblastic leukaemia (ALL), which really revolutionized the view of the scientific world on this small organism as a cancer disease model [2]. In the ensuing 10 years, many models of oncogene induced cancer have been generated in zebrafish along with mutagenesis strategies to identify novel tumour suppressor genes or chromosome instability loci [3–5]. The utility of such models to answer key biological questions continues to grow. In this paper, we focus on developments in the field of myelopoiesis in the zebrafish, cancer models affecting the myeloid lineages, and how these have instructed our knowledge on the biology of these diseases. 2. Zebrafish Myeloid Development Zebrafish haematopoiesis occurs in two waves in the developing embryo, termed primitive and definitive [6]. In contrast to human and murine haematopoiesis (where primitive haematopoiesis initiates with the development of primitive erythroid cells in the blood islands

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