Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia - Archive ouverte HAL Access content directly
Journal Articles Blood Year : 2011

Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia

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Mélanie Bonnet
  • Function : Author
Marie Loosveld
Bertrand Montpellier
  • Function : Author
Jean-Marc Navarro
  • Function : Author
Benoit Quilichini
  • Function : Author
Christophe Picard
Julie Di Cristofaro
Claude Bagnis
  • Function : Author
Chantal Fossat
  • Function : Author
Lucie Hernandez
  • Function : Author
  • PersonId : 764619
  • IdRef : 168705060
Sandrine Roulland
Ester Morgado
  • Function : Author
Christine Formisano-Tréziny
  • Function : Author
Willem Dik
  • Function : Author
Anton Langerak
Thomas Prebet
  • Function : Author
Norbert Vey
Gérard Michel
  • Function : Author
Jean Gabert
  • Function : Author
Jean Soulier
  • Function : Author
Elizabeth Macintyre
Vahid Asnafi
  • Function : Author
Dominique Payet-Bornet
Bertrand Nadel
  • Function : Author

Abstract

Abstract 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 posttranscriptional 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 NOTCH1m might play a dual transcriptional and posttranscriptional 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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Dates and versions

hal-03606489 , version 1 (11-03-2022)

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Mélanie Bonnet, Marie Loosveld, Bertrand Montpellier, Jean-Marc Navarro, Benoit Quilichini, et al.. Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia. Blood, 2011, 117 (24), pp.6650-6659. ⟨10.1182/blood-2011-02-336842⟩. ⟨hal-03606489⟩

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