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Accession IconGSE65382

MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome [Microarray]

Organism Icon Mus musculus
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

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Description
To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulators Zeb1 and Tcf4 significantly reduced leukemic blast invasion. By classifying mouse and human leukemia according to Evi1/EVI1and Erg/ERG expression, reflecting aggressiveness and cell-of-origin and performing comparative transcriptomics we identified numerous EMT-related genes that were significantly associated with poor overall survival of AML patients.
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