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Article: Follistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia

TitleFollistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia
Authors
Keywordsacute myeloid leukemia
animal cell
animal experiment
animal model
animal tissue
Issue Date2020
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1757-4684
Citation
EMBO Molecular Medicine, 2020, v. 12 n. 4, p. article no. e10895 How to Cite?
AbstractInternal tandem duplication of Fms‐like tyrosine kinase 3 (FLT3/ITD) occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor response to conventional treatment and adverse outcome. Here, we reported that human FLT3/ITD expression led to axis duplication and dorsalization in about 50% of zebrafish embryos. The morphologic phenotype was accompanied by ectopic expression of a morphogen follistatin (fst) during early embryonic development. Increase in fst expression also occurred in adult FLT3/ITD‐transgenic zebrafish, Flt3/ITD knock‐in mice, and human FLT3/ITD AML cells. Overexpression of human FST317 and FST344 isoforms enhanced clonogenicity and leukemia engraftment in xenotransplantation model via RET, IL2RA, and CCL5 upregulation. Specific targeting of FST by shRNA, CRISPR/Cas9, or antisense oligo inhibited leukemic growth in vitro and in vivo. Importantly, serum FST positively correlated with leukemia engraftment in FLT3/ITD AML patient‐derived xenograft mice and leukemia blast percentage in primary AML patients. In FLT3/ITD AML patients treated with FLT3 inhibitor quizartinib, serum FST levels correlated with clinical response. These observations supported FST as a novel therapeutic target and biomarker in FLT3/ITD AML.
Persistent Identifierhttp://hdl.handle.net/10722/293756
ISSN
2023 Impact Factor: 9.0
2023 SCImago Journal Rankings: 3.964
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorHe, BA-
dc.contributor.authorYang, N-
dc.contributor.authorMan, CH-
dc.contributor.authorNg, NKL-
dc.contributor.authorCHER, CY-
dc.contributor.authorLEUNG, HC-
dc.contributor.authorKAN, LLH-
dc.contributor.authorCHENG, BYL-
dc.contributor.authorLAM, SSY-
dc.contributor.authorWang, MLL-
dc.contributor.authorZhang, CX-
dc.contributor.authorKwok, H-
dc.contributor.authorCheng, G-
dc.contributor.authorSharma, R-
dc.contributor.authorMa, ACH-
dc.contributor.authorSo, CWE-
dc.contributor.authorKwong, YL-
dc.contributor.authorLeung, AYH-
dc.date.accessioned2020-11-23T08:21:21Z-
dc.date.available2020-11-23T08:21:21Z-
dc.date.issued2020-
dc.identifier.citationEMBO Molecular Medicine, 2020, v. 12 n. 4, p. article no. e10895-
dc.identifier.issn1757-4676-
dc.identifier.urihttp://hdl.handle.net/10722/293756-
dc.description.abstractInternal tandem duplication of Fms‐like tyrosine kinase 3 (FLT3/ITD) occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor response to conventional treatment and adverse outcome. Here, we reported that human FLT3/ITD expression led to axis duplication and dorsalization in about 50% of zebrafish embryos. The morphologic phenotype was accompanied by ectopic expression of a morphogen follistatin (fst) during early embryonic development. Increase in fst expression also occurred in adult FLT3/ITD‐transgenic zebrafish, Flt3/ITD knock‐in mice, and human FLT3/ITD AML cells. Overexpression of human FST317 and FST344 isoforms enhanced clonogenicity and leukemia engraftment in xenotransplantation model via RET, IL2RA, and CCL5 upregulation. Specific targeting of FST by shRNA, CRISPR/Cas9, or antisense oligo inhibited leukemic growth in vitro and in vivo. Importantly, serum FST positively correlated with leukemia engraftment in FLT3/ITD AML patient‐derived xenograft mice and leukemia blast percentage in primary AML patients. In FLT3/ITD AML patients treated with FLT3 inhibitor quizartinib, serum FST levels correlated with clinical response. These observations supported FST as a novel therapeutic target and biomarker in FLT3/ITD AML.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1757-4684-
dc.relation.ispartofEMBO Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectacute myeloid leukemia-
dc.subjectanimal cell-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectanimal tissue-
dc.titleFollistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia-
dc.typeArticle-
dc.identifier.emailYang, N: yangning@hku.hk-
dc.identifier.emailMan, CH: csman729@hku.hk-
dc.identifier.emailNg, NKL: kalamng@hku.hk-
dc.identifier.emailZhang, CX: chunxiao@hku.hk-
dc.identifier.emailKwok, H: hinkwok.cgs@hku.hk-
dc.identifier.emailCheng, G: himwo@hku.hk-
dc.identifier.emailSharma, R: rasharma@hku.hk-
dc.identifier.emailKwong, YL: ylkwong@hkucc.hku.hk-
dc.identifier.emailLeung, AYH: ayhleung@hku.hk-
dc.identifier.authorityMan, CH=rp02543-
dc.identifier.authorityKwong, YL=rp00358-
dc.identifier.authorityLeung, AYH=rp00265-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.15252/emmm.201910895-
dc.identifier.pmid32134197-
dc.identifier.pmcidPMC7136967-
dc.identifier.scopuseid_2-s2.0-85082339245-
dc.identifier.hkuros319795-
dc.identifier.hkuros316310-
dc.identifier.volume12-
dc.identifier.issue4-
dc.identifier.spagearticle no. e10895-
dc.identifier.epagearticle no. e10895-
dc.identifier.isiWOS:000526640800008-
dc.publisher.placeGermany-
dc.relation.erratumdoi:10.15252/emmm.202012911-
dc.identifier.issnl1757-4676-

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