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Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Bendall, Linda and Nemes, Karolina and Sebestyén, Anna and Márk, Ágnes and Hajdu, Melinda and Kenessey, István and Sticz, Tamás and Nagy, Eszter and Barna, Gábor and Váradi, Zsófia and Kovács, Gábor and Kopper, László and Csóka, Monika (2013) Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL). PLoS ONE, 8 (4). e59335. ISSN 1932-6203

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Abstract

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments.

Item Type: Article
Subjects: R Medicine / orvostudomány > RB Pathology / patológia, kórtan
Depositing User: Elvira Rigóné Kálé
Date Deposited: 05 Feb 2014 17:53
Last Modified: 05 Feb 2014 17:53
URI: http://real.mtak.hu/id/eprint/9837

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