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Oncogenic PTEN functions and models in T-cell malignancies
M Tesio1, A Trinquand1, E Macintyre1
1Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants Malades, Paris, France.
Abstract:
PTEN is a protein phosphatase that is crucial to prevent the malignant transformation of T-cells. Although a numerous mechanisms regulate its expression and function, they are often altered in T-cell acute lymphoblastic leukaemias and T-cell lymphomas. As such, PTEN inactivation frequently occurs in these malignancies, where it can be associated with chemotherapy resistance and poor prognosis. Different Pten knockout models recapitulated the development of T-cell leukaemia/lymphoma, demonstrating that PTEN loss is at the center of a complex oncogenic network that sustains and drives tumorigenesis via the activation of multiple signalling pathways. These aspects and their therapeutic implications are discussed in this review.
Insights
PTEN protein phosphatase loss is central to T-cell cancers, driving oncogenic networks and poor prognosis. Understanding PTEN
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- PTEN (Phosphatase and Tensin homolog) is a critical tumor suppressor protein.
- Its function is vital for preventing malignant transformation in T-cells.
- Dysregulation of PTEN is frequently observed in T-cell malignancies.
Purpose of the Study:
- To review the role of PTEN in T-cell acute lymphoblastic leukaemias and lymphomas.
- To discuss the mechanisms of PTEN alteration in these cancers.
- To explore the therapeutic implications of PTEN's role in tumorigenesis.
Main Methods:
- Review of existing literature on PTEN in T-cell malignancies.
- Analysis of data from Pten knockout mouse models.
- Discussion of signaling pathways implicated in PTEN-driven oncogenesis.
Main Results:
- PTEN inactivation is a common event in T-cell leukaemias and lymphomas.
- Loss of PTEN function promotes T-cell transformation and tumorigenesis.
- PTEN alterations are linked to chemotherapy resistance and poor patient outcomes.
Conclusions:
- PTEN loss is a central driver in a complex oncogenic network in T-cell cancers.
- Targeting PTEN pathways may offer therapeutic strategies for these malignancies.
- Further research into PTEN's multifaceted role is crucial for clinical advancements.
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