Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/105826
DC Field | Value | Language |
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dc.contributor | Department of Health Technology and Informatics | - |
dc.creator | Wang, D | - |
dc.creator | Zheng, L | - |
dc.creator | Cheng, BYL | - |
dc.creator | Sin, CF | - |
dc.creator | Li, R | - |
dc.creator | Tsui, SP | - |
dc.creator | Yi, X | - |
dc.creator | Ma, ACH | - |
dc.creator | He, BL | - |
dc.creator | Leung, AYH | - |
dc.creator | Sun, X | - |
dc.date.accessioned | 2024-04-23T04:31:37Z | - |
dc.date.available | 2024-04-23T04:31:37Z | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | http://hdl.handle.net/10397/105826 | - |
dc.language.iso | en | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.rights | © The Author(s) 2023, corrected publication 2023 | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_US |
dc.rights | The following publication Wang, D., Zheng, L., Cheng, B.Y.L. et al. Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia. Oncogene 42, 1272–1281 (2023) is available at https://doi.org/10.1038/s41388-023-02611-y. | en_US |
dc.title | Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 1272 | - |
dc.identifier.epage | 1281 | - |
dc.identifier.volume | 42 | - |
dc.identifier.doi | 10.1038/s41388-023-02611-y | - |
dcterms.abstract | Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce. We generated zebrafish models of IDH2R172K and IDH2R140Q AML and reported their pathologic, functional and transcriptomic features and therapeutic responses to target therapies. Transgenic embryos co-expressing FLT3ITD and IDH2 mutations showed accentuation of myelopoiesis. As these embryos were raised to adulthood, full-blown leukemia ensued with multi-lineage dysplasia, increase in myeloblasts and marrow cellularity and splenomegaly. The leukemia cells were transplantable into primary and secondary recipients and resulted in more aggressive disease. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in T-cell development at embryonic and adult stages. Single-cell transcriptomic analysis revealed increased myeloid skewing, differentiation blockade and enrichment of leukemia-associated gene signatures in both zebrafish models. Tg(Runx1:FLT3ITDIDH2R172K) but not Tg(Runx1:FLT3ITDIDH2R140Q) zebrafish showed an increase in interferon signals at the adult stage. Leukemic phenotypes in both zebrafish could be ameliorated by quizartinib and enasidenib. In conclusion, the zebrafish models of IDH2 mutated AML recapitulated the morphologic, clinical, functional and transcriptomic characteristics of human diseases, and provided the prototype for developing zebrafish leukemia models of other genotypes that would become a platform for high throughput drug screening. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Oncogene, 2023, v. 42, p. 1272-1281 | - |
dcterms.isPartOf | Oncogene | - |
dcterms.issued | 2023 | - |
dc.identifier.scopus | 2-s2.0-85147344433 | - |
dc.identifier.eissn | 1476-5594 | - |
dc.description.validate | 202404 bcch | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_Scopus/WOS | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | Theme-based Research Scheme; Health and Medical Research Fund | en_US |
dc.description.pubStatus | Published | en_US |
dc.description.oaCategory | CC | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
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s41388-023-02611-y.pdf | 5.58 MB | Adobe PDF | View/Open |
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