Stavropoulou, Vaia and Kaspar, Susanne and Brault, Laurent and Sanders, Mathijs A. and Juge, Sabine and Morettini, Stefano and Tzankov, Alexandar and Iacovino, Michelina and Lau, I-Jun and Milne, Thomas A. and Royo, Hélène and Kyba, Michael and Valk, Peter J. M. and Peters, Antoine H. F. M. and Schwaller, Juerg. (2016) MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome. Cancer cell, 30 (1). pp. 43-58.
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Official URL: https://edoc.unibas.ch/62061/
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Abstract
To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients.
| Faculties and Departments: | 03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Kindliche Leukämie (Schwaller) 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Kindliche Leukämie (Schwaller) 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Childhood Leukemia (Schwaller) |
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| UniBasel Contributors: | Schwaller, Jürg |
| Item Type: | Article, refereed |
| Article Subtype: | Research Article |
| ISSN: | 1878-3686 |
| Note: | Publication type according to Uni Basel Research Database: Journal article |
| Identification Number: |
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| Last Modified: | 31 May 2020 17:40 |
| Deposited On: | 31 May 2020 17:40 |
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