Abstract
Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe the first highly- penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)—which these fish also develop. Zebrafish pre-B ALL shares in vivo features and expression profiles with human pre-B ALL, and these profiles differ from zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant lymphocyte development. As the only robust zebrafish pre-B ALL model and only example where T-ALL also develops, this model can reveal differences between MYC-driven pre-B vs. T-ALL and be exploited to discover novel pre-B ALL therapies.
Highlights
Acute lymphocytic leukemia (ALL), a common cancer and the most prevalent childhood malignancy, comprises >25% of pediatric neoplasia in the U.S, with ~85% being pre-BThese authors contributed : Gilseung Park, Clay Foster.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.ALL [1, 2]
Human MYC induces two zebrafish ALL types with distinct expression signatures Mammalian Myc/MYC transgenes driven by a D. rerio rag2 promoter induce zebrafish T cell ALL (T-ALL) [6, 10]
To study T-ALL in our system, we performed RNA microarray on FACS-purified GFP+ cells dissected from the bodies of 10 hMYC;GFP fish and 3 hlk fish [9], another zebrafish T-ALL model
Summary
Acute lymphocytic leukemia (ALL), a common cancer and the most prevalent childhood malignancy, comprises >25% of pediatric neoplasia in the U.S, with ~85% being pre-B. These authors contributed : Gilseung Park, Clay Foster. Zebrafish (Danio rerio) provide one potential solution, since they can model human leukemias accurately [4], have practical advantages (genetic tractability, high-throughput screens, cost), and share hematopoietic, oncogenic, and tumor suppressive pathways with humans [5]. These features permitted the creation of several zebrafish T cell ALL (T-ALL) models that mimic the human disease [6,7,8,9,10], which subsequently led to key findings in T-ALL genetics, disease progression mechanisms, and signaling [11,12,13,14,15,16], as well as facilitating screens for new treatment agents [17, 18]
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