Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

• Published in: Leukemia Vol. 33; no. 2; pp. 333 - 347
• Main Authors: Borga, Chiara, Park, Gilseung, Foster, Clay, Burroughs-Garcia, Jessica, Marchesin, Matteo, Shah, Rikin, Hasan, Ameera, Ahmed, Syed T., Bresolin, Silvia, Batchelor, Lance, Scordino, Teresa, Miles, Rodney R., te Kronnie, Geertruy, Regens, James L., Frazer, J. Kimble
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group
• Subjects: 13/31; 13/51; 14/32; 14/63; 38/1; 38/39; 38/61; 38/77; 631/67/1990/283/2125; 631/67/395; 631/67/70; 64/116; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Animal genetic engineering; Animals; Animals, Genetically Modified; B cells; Cancer; Cancer Research; Carcinogenesis; Care and treatment; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Childhood cancer; Critical Care Medicine; Danio rerio; Development and progression; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic engineering; Health aspects; Hematology; Humans; Intensive; Internal Medicine; Leukemia; Lubricants; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytic leukemia; Lymphopoiesis; Medicine; Medicine & Public Health; Myc protein; Neoplasms, Multiple Primary - genetics; Neoplasms, Multiple Primary - metabolism; Neoplasms, Multiple Primary - pathology; Oncogenes; Oncology; Pediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; T cells; Tumorigenesis; Zebrafish
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-018-0226-6

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.