| Literature DB >> 27344946 |
Vaia Stavropoulou1, Susanne Kaspar2, Laurent Brault1, Mathijs A Sanders3, Sabine Juge1, Stefano Morettini4, Alexandar Tzankov5, Michelina Iacovino6, I-Jun Lau7, Thomas A Milne7, Hélène Royo4, Michael Kyba8, Peter J M Valk3, Antoine H F M Peters9, Juerg Schwaller10.
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.Entities:
Keywords: EMT; MLL-AF9; acute myeloid leukemia; invasion; poor overall survival; stem cell
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Year: 2016 PMID： 27344946 DOI： 10.1016/j.ccell.2016.05.011
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743