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The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response

1
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
2
Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
3
Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 629; https://doi.org/10.3390/cancers11050629
Received: 22 March 2019 / Revised: 16 April 2019 / Accepted: 4 May 2019 / Published: 6 May 2019
(This article belongs to the Special Issue PTEN: A Multifaceted Tumor Suppressor)
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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer that comprises 10–15% of pediatric and ~25% of adult ALL cases. Although the curative rates have significantly improved over the past 10 years, especially in pediatric patients, T-ALL remains a challenge from a therapeutic point of view, due to the high number of early relapses that are for the most part resistant to further treatment. Considerable advances in the understanding of the genes, signaling networks, and mechanisms that play crucial roles in the pathobiology of T-ALL have led to the identification of the key drivers of the disease, thereby paving the way for new therapeutic approaches. PTEN is critical to prevent the malignant transformation of T-cells. However, its expression and functions are altered in human T-ALL. PTEN is frequently deleted or mutated, while PTEN protein is often phosphorylated and functionally inactivated by casein kinase 2. Different murine knockout models recapitulating the development of T-ALL have demonstrated that PTEN abnormalities are at the hub of an intricate oncogenic network sustaining and driving leukemia development by activating several signaling cascades associated with drug-resistance and poor outcome. These aspects and their possible therapeutic implications are highlighted in this review. View Full-Text
Keywords: lipid phosphatase; PI3K/Akt/mTOR; genetic anomalies; targeted therapy; prognosis lipid phosphatase; PI3K/Akt/mTOR; genetic anomalies; targeted therapy; prognosis
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Martelli, A.M.; Paganelli, F.; Fazio, A.; Bazzichetto, C.; Conciatori, F.; McCubrey, J.A. The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response. Cancers 2019, 11, 629.

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