Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T‐cell lymphoblastic leukemia
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Le résumé fourni par la source
Abstract T‐lineage acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological malignancy that accounts for 10%–15% of pediatric and 25% of adult ALL cases. Although the prognosis of T‐ALL has improved over time, the outcome of T‐ALL patients with primary resistant or relapsed leukemia remains poor. Therefore, further progress in the treatment of T‐ALL requires a better understanding of its biology and the development of more effective precision oncologic therapies. The proto‐oncogene MYB is highly expressed in diverse hematologic malignancies, including T‐ALLs with genomic aberrations that further potentiate its expression and activity. Previous studies have associated MYB with a malignant role in the pathogenesis of several cancers. However, its role in the induction and maintenance of T‐ALL remains relatively poorly understood. In this study, we found that an increased copy number of MYB is associated with higher MYB expression levels, and might be associated with inferior event‐free survival of pediatric T‐ALL patients. Using our previously described conditional Myb overexpression mice, we generated two distinct MYB‐driven T‐ALL mouse models. We demonstrated that the overexpression of Myb synergizes with Pten deletion but not with the overexpression of Lmo2 to accelerate the development of T‐cell lymphoblastic leukemias. We also showed that MYB is a dependency factor in T‐ALL since RNA interference of Myb blocked cell cycle progression and induced apoptosis in both human and murine T‐ALL cell lines. Finally, we provide preclinical evidence that targeting the transcriptional activity of MYB can be a useful therapeutic strategy for the treatment of T‐ALL.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <i>Myb</i> overexpression synergizes with the loss of <i>Pten</i> and is a dependency factor and therapeutic target in T‐cell lymphoblastic leukemia
- Date Crossref
- 01/03/2024
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Ghent University Hospital Normal and Malignant Hematopoiesis Lab pays non établi dans la noticeÉtablissement de santé
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Cancer Research Institute Ghent pays non établi dans la noticeStructure de recherche
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University of Parma Department of Medicine and Surgery pays non établi dans la noticeUniversité ou école supérieure
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University of Perugia Institute of Hematology and Center for Hemato-Oncology Research pays non établi dans la noticeUniversité ou école supérieure
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Ghent University Normal and Malignant Hematopoiesis Lab pays non établi dans la noticeUniversité ou école supérieure
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Memorial Sloan Kettering Cancer Center Tow Center for Developmental Oncology pays non établi dans la noticeÉtablissement de santé
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Sloan Kettering Institute and Department of Pediatrics Tow Center for Developmental Oncology pays non établi dans la noticeStructure de recherche
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Steven Goossens pays non établi dans la noticeInstitution
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Deceased in 2022. An exceptional scientist and individual whose absence is deeply felt pays non établi dans la noticeInstitution
Normal and Malignant Hematopoiesis Lab — Ghent University Hospital, Cancer Research Institute Ghent et Department of Medicine and Surgery — University of Parma, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.