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https://ahro.austin.org.au/austinjspui/handle/1/19152| Title: | Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia. | Austin Authors: | Ghisi, Margherita;Kats, Lev;Masson, Frederic;Li, Jason;Kratina, Tobias;Vidacs, Eva;Gilan, Omer;Doyle, Maria A;Newbold, Andrea;Bolden, Jessica E;Fairfax, Kirsten A;de Graaf, Carolyn A;Firth, Matthew;Zuber, Johannes;Dickins, Ross A;Corcoran, Lynn M;Dawson, Mark A;Belz, Gabrielle T;Johnstone, Ricky W | Affiliation: | School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 Victoria, Australia Cancer Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr-Gasse 7, 1030 Vienna, Austria Australian Centre for Blood Diseases, Monash University, Melbourne, 3004 Victoria, Australia Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 Victoria, Australia Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia Bioinformatics Core, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, Australia Research Computing Facility, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, Australia Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia |
Issue Date: | 11-Jul-2016 | Date: | 2016-06-30 | Publication information: | Cancer cell 2016; 30(1): 59-74 | Abstract: | E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8;21) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/19152 | DOI: | 10.1016/j.ccell.2016.05.019 | Journal: | Cancer cell | PubMed URL: | 27374225 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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