Several reports suggest that PI3k/Akt pathway can be activated in childhood ALL. Rapamycin suppresses oncogenic processes sustained by PI3k/Akt, therefore we investigated whether it could affect blast survival. We found that rapamycin induced apoptosis of blasts in 56% of the bone marrow samples analysed. The block of phosphatidyl-inositol pathway appeared as being involved in the activation of the death program of malignant lymphoblasts, as suggested by using the specific PI3k inhibitor, wortmannin. Consistently, high expression levels of phospho-Akt were detected in samples responsive to rapamycin. Moreover, rapamycin synergically cooperated with doxorubicin in inducing apoptosis, even in non responder samples. Anthracyclines activate NF-
Rapamycin stimulates apoptosis of Childhood Acute Lymphoblastic Leukemia Cells / Avellino, R.; Romano, S.; Parasole, R.; Bisogni, Rita; Lamberti, Annalisa; Poggi, V.; Romano, MARIA FIAMMETTA. - In: BLOOD. - ISSN 0006-4971. - ELETTRONICO. - 106:(2005), pp. 1400-1406.
Rapamycin stimulates apoptosis of Childhood Acute Lymphoblastic Leukemia Cells
ROMANO S.;BISOGNI, RITA;LAMBERTI, ANNALISA;ROMANO, MARIA FIAMMETTA
2005
Abstract
Several reports suggest that PI3k/Akt pathway can be activated in childhood ALL. Rapamycin suppresses oncogenic processes sustained by PI3k/Akt, therefore we investigated whether it could affect blast survival. We found that rapamycin induced apoptosis of blasts in 56% of the bone marrow samples analysed. The block of phosphatidyl-inositol pathway appeared as being involved in the activation of the death program of malignant lymphoblasts, as suggested by using the specific PI3k inhibitor, wortmannin. Consistently, high expression levels of phospho-Akt were detected in samples responsive to rapamycin. Moreover, rapamycin synergically cooperated with doxorubicin in inducing apoptosis, even in non responder samples. Anthracyclines activate NF-I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
