Abstract
The recent advent of next-generation sequencing (NGS) has greatly accelerated identification of gene mutations in myeloid malignancies at unprecedented speed that will soon outpace their functional validation by conventional laboratory techniques and animal models. A high-throughput whole-organism model is useful for the functional validation of new mutations. We recently reported the use of zebrafish to evaluate the hematopoietic function of isocitrate dehydrogenase 1 (IDH1) and the effects of expressing human IDH1-R132H that is frequently identified in human acute myeloid leukemia (AML), in myelopoiesis, with a view to develop zebrafish as a model of AML. Here, we use IDH1 as an example to describe a comprehensive approach to evaluate hematopoietic gene function and the effects of mutations using zebrafish as a model.
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References
Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361(11):1058–1066
Ley TJ, Ding L, Walter MJ et al (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363(25):2424–2433
Patel JP, Gonen M, Figueroa ME et al (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366(12):1079–1089
Cancer Genome Atlas Research Network (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074
Martin CS, Moriyama A, Zon LI (2011) Hematopoietic stem cells, hematopoiesis and disease: lessons from the zebrafish model. Genome Med 3(12):83
de Jong JL, Zon LI (2005) Use of the zebrafish system to study primitive and definitive hematopoiesis. Annu Rev Genet 39:481–501
Davidson AJ, Zon LI (2004) The ‘definitive’ (and ‘primitive’) guide to zebrafish hematopoiesis. Oncogene 23(43):7233–7246
Paw BH, Zon LI (2000) Zebrafish: a genetic approach in studying hematopoiesis. Curr Opin Hematol 7(2):79–84
Im AP, Sehgal AR, Carroll MP et al (2014) DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia 28(9):1774–1783
Lasho TL, Jimma T, Finke CM et al (2012) SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood 120(20):4168–4171
Pardanani A, Patnaik MM, Lasho TL et al (2010) Recurrent IDH mutations in high-risk myelodysplastic syndrome or acute myeloid leukemia with isolated del(5q). Leukemia 24(7):1370–1372
Caramazza D, Lasho TL, Finke CM et al (2010) IDH mutations and trisomy 8 in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 24(12):2120–2122
Sasaki M, Knobbe CB, Munger JC et al (2012) IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488(7413):656–659
Shi X, He BL, Ma AC et al (2015) Functions of idh1 and its mutation in the regulation of developmental hematopoiesis in zebrafish. Blood 125(19):2974–2984
Cermak T, Doyle EL, Christian M et al (2011) Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 39(12):e82
He BL, Shi X, Man CH, Ma AC et al (2014) Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. Blood 123(16):2518–2529
Ma AC, Chung MI, Liang R et al (2010) A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos. Leukemia 24(12):2090–2099
Ma AC, Fan A, Ward AC et al (2009) A novel zebrafish jak2a(V581F) model shared features of human JAK2(V617F) polycythemia vera. Exp Hematol 37(12):1379.e4–1386.e4
Ma AC, Chung MI, Liang R et al (2009) The role of survivin2 in primitive hematopoiesis during zebrafish development. Leukemia 23(4):712–720
Ma AC, Ward AC, Liang R et al (2007) The role of jak2a in zebrafish hematopoiesis. Blood 110(6):1824–1830
Ma A, Lin R, Chan PK et al (2007) The role of survivin in angiogenesis during zebrafish embryonic development. BMC Dev Biol 7:50
Ma AC, Liang R, Leung AY (2007) The role of phospholipase C gamma 1 in primitive hematopoiesis during zebrafish development. Exp Hematol 35(3):368–373
Jin H, Li L, Xu J et al (2012) Runx1 regulates embryonic myeloid fate choice in zebrafish through a negative feedback loop inhibiting Pu.1 expression. Blood 119(22):5239–5249
Renshaw SA, Loynes CA, Trushell DM et al (2006) A transgenic zebrafish model of neutrophilic inflammation. Blood 108(13):3976–3978
Ma AC, Lee HB, Clark KJ et al (2013) High efficiency in vivo genome engineering with a simplified 15-RVD GoldyTALEN design. PLoS One 8(5):e65259
Kobayashi I, Kobayashi-Sun J, Kim AD et al (2014) Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling. Nature 512(7514):319–323
Stachura DL, Reyes JR, Bartunek P et al (2009) Zebrafish kidney stromal cell lines support multilineage hematopoiesis. Blood 114(2):279–289
Nakade S, Tsubota T, Sakane Y et al (2014) Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9. Nat Commun 5:5560
Neff KL, Argue DP, Ma AC et al (2013) Mojo hand, a TALEN design tool for genome editing applications. BMC Bioinformatics 14:1
Acknowledgments
Zebrafish research was supported by Faculty Core Zebrafish Facility, LKS Faculty of Medicine, HKU. This work was supported by HKU771613M, HKUST5/CRF/12R, CityU9/CRF/13G, HMRF02132326, HMRF03143756 and HKU Seed Funding for Basic Research (201401159004, 201411159098). AYHL is the Li Shu Fan Medical Foundation Professor in Haematology and received funding from its endowment.
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Ma, A.C.H., Shi, X., He, BL., Guo, Y., Leung, A.Y.H. (2017). A Zebrafish Model for Evaluating the Function of Human Leukemic Gene IDH1 and Its Mutation. In: Fortina, P., Londin, E., Park, J., Kricka, L. (eds) Acute Myeloid Leukemia. Methods in Molecular Biology, vol 1633. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7142-8_13
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DOI: https://doi.org/10.1007/978-1-4939-7142-8_13
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