کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2106704 1083620 2016 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome
چکیده انگلیسی


• Generation of an inducible and reversible mouse model for MLL-AF9-driven AML
• The cell of origin controls aggressiveness and outcome of MLL-AF9-mediated AML
• The EMT transcription factor ZEB1 controls AML cell migration and invasion
• Expression of multiple EMT-related genes is associated with poor outcome in human AML

SummaryTo 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 30, Issue 1, 11 July 2016, Pages 43–58
نویسندگان
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