Zebrafish have emerged as a powerful model of development and cancer. Human, mouse, and zebrafish malignancies exhibit striking histopathologic and molecular similarities, underscoring the remarkable conservation of genetic pathways required to induce cancer. Zebrafish are uniquely suited for large-scale studies in which hundreds of animals can be used to investigate cancer processes. Moreover, zebrafish are small in size, optically clear during development, and amenable to genetic manipulation. Facile transgenic approaches and new technologies in gene inactivation have provided much needed genomic resources to interrogate the function of specific oncogenic and tumor suppressor pathways in cancer. This manuscript focuses on the unique attribute of labeling leukemia cells with fluorescent proteins and directly visualizing cancer processes in vivo including tumor growth, dissemination, and intravasation into the vasculature. We will also discuss the use of fluorescent transgenic approaches and cell transplantation to assess leukemia-propagating cell frequency and response to chemotherapy. 1. Zebrafish Models of Leukemia Zebrafish models of hematological malignancies exhibit striking similarities with human and mouse disease [1–7], yet afford unique avenues of study due to imaging modalities that permit direct visualization of fluorescently labeled blood cells within live animals. As with mouse and human disease, zebrafish leukemias are distinguished from lymphomas by the infiltration of leukemic cells into the marrow. Lymphomas are predominantly located as masses throughout the body, including lymph nodes in mouse and human, and have no or little infiltration into the marrow [8]. Leukemias are also classified as acute or chronic. Acute leukemias are arrested at early stages of maturation, are highly proliferative, and advance quickly in patients [8]. By contrast, chronic leukemias are arrested at later stages of maturation and resemble functional, yet abnormal, blood cell counterparts. Although characterized by increased circulating white blood counts, chronic leukemias are often much slower growing and take months or years to progress. Leukemias can be further subdivided based on the blood lineage in which cells have become transformed [8]. To date, zebrafish models of Acute Lymphoblastic Leukemias (ALL), Acute Myeloid Leukemia (AML), and Myeloproliferative Neoplasms (MPN) have been described. Zebrafish first emerged as a powerful genetic model of leukemia with the description of transgenic approaches in which cMYC was overexpressed in developing
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