The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response
Martelli, Alberto M.; Paganelli, Francesca; Fazio, Antonietta; Bazzichetto, Chiara; Conciatori, Fabiana; McCubrey, James A.
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.
Martelli, Alberto M., & Paganelli, Francesca, & Fazio, Antonietta, & Bazzichetto, Chiara, & Conciatori, Fabiana, & McCubrey, James A.. (May 2019). The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response. Cancers, (11:5), p.629. Retrieved from http://hdl.handle.net/10342/8339
Martelli, Alberto M., and Paganelli, Francesca, and Fazio, Antonietta, and Bazzichetto, Chiara, and Conciatori, Fabiana, and McCubrey, James A.. "The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response". Cancers. 11:5. (629.), May 2019. October 31, 2020. http://hdl.handle.net/10342/8339.
Martelli, Alberto M. and Paganelli, Francesca and Fazio, Antonietta and Bazzichetto, Chiara and Conciatori, Fabiana and McCubrey, James A., "The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response," Cancers 11, no. 5 (May 2019), http://hdl.handle.net/10342/8339 (accessed October 31, 2020).
Martelli, Alberto M., Paganelli, Francesca, Fazio, Antonietta, Bazzichetto, Chiara, Conciatori, Fabiana, McCubrey, James A.. The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response. Cancers. May 2019; 11(5) 629. http://hdl.handle.net/10342/8339. Accessed October 31, 2020.