VENTX induces expansion of primitive erythroid cells and contributes to the development of acute myeloid leukemia in mice
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// Eva Gentner 1 , Naidu M. Vegi 1 , Medhanie A. Mulaw 1 , Tamoghna Mandal 1 , Shiva Bamezai 1 , Rainer Claus 2 , Alpaslan Tasdogan 3 , Leticia Quintanilla-Martinez 4 , Alexander Grunenberg 5 , Konstanze Döhner 5 , Hartmut Döhner 5 , Lars Bullinger 5 , Torsten Haferlach 6 , Christian Buske 1 , Vijay P.S. Rawat 1, * , Michaela Feuring-Buske 5, * 1 Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany 2 Department of Internal Medicine I, University Hospital Freiburg, 79106 Freiburg, Germany 3 Institute of Immunology, Ulm University, 89081 Ulm, Germany 4 Institute of Pathology, University of Tübingen, 72076 Tübingen, Germany 5 Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany 6 MLL Munich Leukemia Laboratory, 81377 Munich, Germany * These authors have contributed equally to this work Correspondence to: Michaela Feuring-Buske, email: michaela.feuring-buske@uni-ulm.de Keywords: acute erythroleukemia, VENTX, AML1-ETO, homeobox gene, embryonic transcription factor Received: August 12, 2016 Accepted: November 09, 2016 Published: November 24, 2016 ABSTRACT Homeobox genes are key regulators in normal and malignant hematopoiesis. The human Vent-like homeobox gene VENTX , a putative homolog of the Xenopus laevis Xvent-2 gene, was shown to be highly expressed in normal myeloid cells and in patients with acute myeloid leukemia. We now demonstrate that constitutive expression of VENTX suppresses expression of genes responsible for terminal erythroid differentiation in normal CD34 + stem and progenitor cells. Transplantation of bone marrow progenitor cells retrovirally engineered to express VENTX caused massive expansion of primitive erythroid cells and partly acute erythroleukemia in transplanted mice. The leukemogenic potential of VENTX was confirmed in the AML1-ETO transplantation model, as in contrast to AML1-ETO alone co-expression of AML1-ETO and VENTX induced acute myeloid leukemia, partly expressing erythroid markers, in all transplanted mice. VENTX was highly expressed in patients with primary human erythroleukemias and knockdown of VENTX in the erythroleukemic HEL cell line significantly blocked cell growth. In summary, these data indicate that VENTX is able to perturb erythroid differentiation and to contribute to myeloid leukemogenesis when co-expressed with appropriate AML oncogenes and point to its potential significance as a novel therapeutic target in AML.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- VENTX induces expansion of primitive erythroid cells and contributes to the development of acute myeloid leukemia in mice
- Date Crossref
- 24/11/2016
- Éditeur
- Impact Journals, LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University Hospital Ulm Department of Internal Medicine III pays non établi dans la noticeÉtablissement de santé
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University Medical Center Freiburg pays non établi dans la noticeÉtablissement de santé
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Universität Ulm pays non établi dans la noticeUniversité ou école supérieure
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University of Tübingen Institute of Pathology pays non établi dans la noticeUniversité ou école supérieure
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Munich Leukemia Laboratory (Germany) pays non établi dans la noticeEntreprise
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CCC and University Hospital of Ulm Institute of Experimental Cancer Research pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Freiburg Department of Internal Medicine I pays non établi dans la noticeUniversité ou école supérieure
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Ulm University Institute of Immunology pays non établi dans la noticeUniversité ou école supérieure
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MLL Munich Leukemia Laboratory pays non établi dans la noticeStructure de recherche
Department of Internal Medicine III — University Hospital Ulm, University Medical Center Freiburg et Universität Ulm, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.