| Post-transcriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia. | |
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MedLine Citation:
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PMID: 21527520 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cumulative evidence indicates that MYC, one of the major downstream effectors of NOTCH1, is a critical component of T-cell acute lymphoblastic leukemia (T-ALL) oncogenesis and a potential candidate for targeted therapy. However, MYC is a complex oncogene, involving both fine protein dosage and cell-context dependency, and detailed understanding of MYC-mediated oncogenesis in T-ALL is still lacking. To better understand how MYC is interspersed in the complex T-ALL oncogenic networks, we performed a thorough molecular and biochemical analysis of MYC activation in a comprehensive collection of primary adult and pediatric patient samples. We find that MYC expression is highly variable, and that high MYC expression levels can be generated in a large number of cases in absence of NOTCH1/FBXW7 mutations, suggesting the occurrence of multiple activation pathways in addition to NOTCH1. Furthermore, we show that post-transcriptional deregulation of MYC constitutes a major alternative pathway of MYC activation in T-ALL, operating partly via the PI3K/AKT axis through down-regulation of PTEN, and that NOTCH1(m) might play a dual transcriptional and post-transcriptional role in this process. Altogether, our data lend further support to the significance of therapeutic targeting of MYC and/or the PTEN/AKT pathways, both in GSI-resistant and identified NOTCH1-independent/MYC-mediated T-ALL patients. |
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Authors:
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Mélanie Bonnet; Marie Loosveld; Bertrand Montpellier; Jean-Marc Navarro; Benoit Quilichini; Christophe Picard; Julie Di Cristofaro; Claude Bagnis; Chantal Fossat; Lucie Hernandez; Emilie Mamessier; Sandrine Roulland; Ester Morgado; Christine Formisano-Tréziny; Willem A Dik; Anton W Langerak; Thomas Prebet; Norbert Vey; Gérard Michel; Jean Gabert; Jean Soulier; Elizabeth A Macintyre; Vahid Asnafi; Dominique Payet-Bornet; Bertrand Nadel |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-28 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Center of Immunology of Marseille Luminy, Universite de la Mediterranee, Marseille, France; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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