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Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia

(2024) HEMASPHERE. 8(3).
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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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MLA
Pedro Pinto De Almeida, André, et al. “Myb Overexpression Synergizes with the Loss of Pten and Is a Dependency Factor and Therapeutic Target in T-Cell Lymphoblastic Leukemia.” HEMASPHERE, vol. 8, no. 3, 2024, doi:10.1002/hem3.51.
APA
Pedro Pinto De Almeida, A., T’Sas, S., Pagliaro, L., Fijalkowski, I., Sleeckx, W., Van Steenberge, H., … Pieters, T. (2024). Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia. HEMASPHERE, 8(3). https://doi.org/10.1002/hem3.51
Chicago author-date
Pedro Pinto De Almeida, André, Sara T’Sas, Luca Pagliaro, Igor Fijalkowski, Wouter Sleeckx, Hannah Van Steenberge, Raffaella Zamponi, et al. 2024. “Myb Overexpression Synergizes with the Loss of Pten and Is a Dependency Factor and Therapeutic Target in T-Cell Lymphoblastic Leukemia.” HEMASPHERE 8 (3). https://doi.org/10.1002/hem3.51.
Chicago author-date (all authors)
Pedro Pinto De Almeida, André, Sara T’Sas, Luca Pagliaro, Igor Fijalkowski, Wouter Sleeckx, Hannah Van Steenberge, Raffaella Zamponi, Béatrice Lintermans, Wouter Van Loocke, Bruno Palhais, Alexandra Reekmans, Valentina Bardelli, Lisa Demoen, Lindy Reunes, Dieter Deforce, Filip Van Nieuwerburgh, Alex Kentsis, Panagiotis Ntziachristos, Nadine Van Roy, Barbara De Moerloose, Cristina Mecucci, Roberta La Starza, Giovanni Roti, Steven Goossens, Pieter Van Vlierberghe, and Tim Pieters. 2024. “Myb Overexpression Synergizes with the Loss of Pten and Is a Dependency Factor and Therapeutic Target in T-Cell Lymphoblastic Leukemia.” HEMASPHERE 8 (3). doi:10.1002/hem3.51.
Vancouver
1.
Pedro Pinto De Almeida A, T’Sas S, Pagliaro L, Fijalkowski I, Sleeckx W, Van Steenberge H, et al. Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia. HEMASPHERE. 2024;8(3).
IEEE
[1]
A. Pedro Pinto De Almeida et al., “Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia,” HEMASPHERE, vol. 8, no. 3, 2024.
@article{01HSDDKNT1VJ91BW09BZRBJS65,
  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.}},
  articleno    = {{e51}},
  author       = {{Pedro Pinto De Almeida, André and T'Sas, Sara and Pagliaro, Luca and Fijalkowski, Igor and Sleeckx, Wouter and Van Steenberge, Hannah and  Zamponi, Raffaella and Lintermans, Béatrice and Van Loocke, Wouter and Palhais, Bruno and Reekmans, Alexandra and  Bardelli, Valentina and Demoen, Lisa and Reunes, Lindy and Deforce, Dieter and Van Nieuwerburgh, Filip and  Kentsis, Alex and Ntziachristos, Panagiotis and Van Roy, Nadine and De Moerloose, Barbara and  Mecucci, Cristina and  La Starza, Roberta and  Roti, Giovanni and Goossens, Steven and Van Vlierberghe, Pieter and Pieters, Tim}},
  issn         = {{2572-9241}},
  journal      = {{HEMASPHERE}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{18}},
  title        = {{Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T-cell lymphoblastic leukemia}},
  url          = {{http://doi.org/10.1002/hem3.51}},
  volume       = {{8}},
  year         = {{2024}},
}

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