{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:33:44Z","timestamp":1772156024129,"version":"3.50.1"},"reference-count":55,"publisher":"The Royal Society","issue":"10","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"name":"Technical Service Center"},{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"crossref"}]},{"name":"School of Life Sciences & Biotechnology, Shanghai Jiao Tong University"},{"name":"Dr. Leonard Zon"},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"crossref","award":["WH101117001"],"award-info":[{"award-number":["WH101117001"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>\n                    <jats:italic>HOXA9<\/jats:italic>\n                    and\n                    <jats:italic>MEIS1<\/jats:italic>\n                    are co-expressed in over 50% of acute myeloid leukaemia (AML) and play essential roles in leukaemogenesis, but the mechanisms involved are poorly understood. Diverse animal models offer valuable tools to recapitulate different aspects of AML and link\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies to clinical trials. We generated a double transgenic zebrafish that enables\n                    <jats:italic>hoxa9<\/jats:italic>\n                    overexpression in blood cells under the draculin (\n                    <jats:italic>drl<\/jats:italic>\n                    ) regulatory element and an inducible expression of\n                    <jats:italic>meis1<\/jats:italic>\n                    through a heat shock promoter. After induction, Tg(\n                    <jats:italic>drl<\/jats:italic>\n                    :\n                    <jats:italic>hoxa9<\/jats:italic>\n                    ;\n                    <jats:italic>hsp70<\/jats:italic>\n                    :\n                    <jats:italic>meis1<\/jats:italic>\n                    ) embryos developed a preleukaemic state with reduced myeloid and erythroid differentiation coupled with the poor production of haematopoietic stem cells and myeloid progenitors. Importantly, most adult Tg(\n                    <jats:italic>drl<\/jats:italic>\n                    :\n                    <jats:italic>hoxa9<\/jats:italic>\n                    ;\n                    <jats:italic>hsp70<\/jats:italic>\n                    :\n                    <jats:italic>meis1<\/jats:italic>\n                    ) fish at 3 months old showed abundant accumulations of immature myeloid precursors, interrupted differentiation and anaemia in the kidney marrow, and infiltration of myeloid precursors in peripheral blood, resembling human AML. Genome-wide transcriptional analysis also confirmed AML transformation by the transgene. Moreover, the dihydroorotate dehydrogenase (DHODH) inhibitor that reduces leukaemogenesis in mammals effectively restored haematopoiesis in Tg(\n                    <jats:italic>drl<\/jats:italic>\n                    :\n                    <jats:italic>hoxa9<\/jats:italic>\n                    ;\n                    <jats:italic>hsp70<\/jats:italic>\n                    :\n                    <jats:italic>meis1<\/jats:italic>\n                    ) embryos and improved their late survival. Thus, Tg(\n                    <jats:italic>drl<\/jats:italic>\n                    :\n                    <jats:italic>hoxa9<\/jats:italic>\n                    ;\n                    <jats:italic>hsp70<\/jats:italic>\n                    :\n                    <jats:italic>meis1<\/jats:italic>\n                    ) zebrafish is a rapid-onset high-penetrance AML-like disease model, which provides a novel tool to harness the unique advantages of zebrafish for mechanistic studies and drug screening against\n                    <jats:italic>HOXA9<\/jats:italic>\n                    \/\n                    <jats:italic>MEIS1<\/jats:italic>\n                    overexpressed high-risk AML.\n                  <\/jats:p>","DOI":"10.1098\/rsob.220172","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T03:07:11Z","timestamp":1666753631000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>Hoxa9<\/i>\n                    \/\n                    <i>meis1<\/i>\n                    -transgenic zebrafish develops acute myeloid leukaemia-like disease with rapid onset and high penetrance"],"prefix":"10.1098","volume":"12","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongji","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengling","family":"Huang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Core facility and technical service center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-511X","authenticated-orcid":true,"given":"Lili","family":"Jing","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.10"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.057"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00425-3"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes10080614"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00495-3"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01632"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1011"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.147"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00297"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00115"},{"key":"e_1_3_7_12_2","first-page":"335","article-title":"Zebrafish models of human leukemia: technological advances and mechanistic insights","volume":"916","author":"Harrison NR","year":"2016","unstructured":"Harrison NR, Laroche FJF, Gutierrez A, Feng H. 2016 Zebrafish models of human leukemia: technological advances and mechanistic insights. 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