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Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells
| Content Provider | Scilit |
|---|---|
| Author | Avellino, Raffaella Romano, Simona Parasole, Rosanna Bisogni, Rita Lamberti, Annalisa Poggi, Vincenzo Venuta, Salvatore Romano, Maria Fiammetta |
| Copyright Year | 2005 |
| Description | The phosphatidyl-inositol 3 kinase (PI3k)/Akt pathway has been implicated in childhood acute lymphoblastic leukemia (ALL). Because rapamycin suppresses the oncogenic processes sustained by PI3k/Akt, we investigated whether rapamycin affects blast survival. We found that rapamycin induces apoptosis of blasts in 56% of the bone marrow samples analyzed. Using the PI3k inhibitor wortmannin, we show that the PI3k/Akt pathway is involved in blast survival. Moreover, rapamycin increased doxorubicin-induced apoptosis even in nonresponder samples. Anthracyclines activate nuclear factor κB (NF-κB), and disruption of this signaling pathway increases the efficacy of apoptogenic stimuli. Rapamycin inhibited doxorubicin-induced NF-κB in ALL samples. Using a short interfering (si) RNA approach, we demonstrate that FKBP51, a large immunophilin inhibited by rapamycin, is essential for drug-induced NF-κB activation in human leukemia. Furthermore, rapamycin did not increase doxorubicin-induced apoptosis when NF-κB was overexpressed. In conclusion, rapamycin targets 2 pathways that are crucial for cell survival and chemoresistance of malignant lymphoblasts—PI3k/Akt through the mammalian target of rapamycin and NF-κB through FKBP51—suggesting that the drug could be beneficial in the treatment of childhood ALL. (Blood. 2005;106:1400-1406) |
| Related Links | http://www.bloodjournal.org/content/106/4/1400.full.pdf |
| Ending Page | 1406 |
| Page Count | 7 |
| Starting Page | 1400 |
| DOI | 10.1182/blood-2005-03-0929 |
| Journal | Blood |
| Issue Number | 4 |
| Volume Number | 106 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2005-08-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Apoptosis Bone Marrow Survival Pi3k/akt Leukemia Rapamycin Childhood Lymphoblastic Efficacy Journal: Blood (Vol- 78, Issue- 4) |
| Content Type | Text |
| Resource Type | Article |
