2016-07-11
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome
Publication
Publication
Cancer Cell , Volume 30 - Issue 1 p. 43- 58
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.
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| doi.org/10.1016/j.ccell.2016.05.011, hdl.handle.net/1765/97606 | |
| Cancer Cell | |
| Organisation | Department of Hematology |
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Stavropoulou, V. (Vaia), Kaspar, S. (Susanne), Brault, L. (Laurent), Sanders, M., Juge, S. (Sabine), Morettini, S. (Stefano), … Schwaller, J. (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), 43–58. doi:10.1016/j.ccell.2016.05.011 |
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