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