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Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia.
Ghisi, Margherita; Kats, Lev; Masson, Frederick; 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.
Afiliação
  • Ghisi M; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, 3004 VIC, Australia. Electronic address: margherita.ghisi@monash.edu.
  • Kats L; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia.
  • Masson F; Cancer Inflammation Laboratory, Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, 3084 VIC, Australia; Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medic
  • Li J; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia; Bioinformatics Core, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia.
  • Kratina T; Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
  • Vidacs E; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia.
  • Gilan O; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia.
  • Doyle MA; Research Computing Facility, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia.
  • Newbold A; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia.
  • Bolden JE; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia; Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052 VIC, Australia.
  • Fairfax KA; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia; Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052 VIC, Australia.
  • de Graaf CA; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia; Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052 VIC, Australia.
  • Firth M; Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
  • Zuber J; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
  • Dickins RA; Australian Centre for Blood Diseases, Monash University, Melbourne, 3004 VIC, Australia.
  • Corcoran LM; Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
  • Dawson MA; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia.
  • Belz GT; Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
  • Johnstone RW; Cancer Therapeutics Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, 3002 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3010 VIC, Australia. Electronic address: ricky.johnstone@petermac.org.
Cancer Cell ; 30(1): 59-74, 2016 07 11.
Article em En | MEDLINE | ID: mdl-27374225
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Translocação Genética / Leucemia Mieloide Aguda / Proteínas de Fusão Oncogênica / Proteína de Leucina Linfoide-Mieloide / Proteína 2 Inibidora de Diferenciação / Proteína 2 Semelhante ao Fator 7 de Transcrição Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Translocação Genética / Leucemia Mieloide Aguda / Proteínas de Fusão Oncogênica / Proteína de Leucina Linfoide-Mieloide / Proteína 2 Inibidora de Diferenciação / Proteína 2 Semelhante ao Fator 7 de Transcrição Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article