We determined the effects of severe hypoxia (B0.1% O2) on acute myeloid leukemia cells expressing the AML1/ETO oncogene. Incubation of Kasumi-1 cells in hypoxia induced growth arrest, apoptosis and reduction of AML1/ETO protein expression. The conditional expression of AML1/ETO in U937-A/E cells showed that hypoxia induces marked apoptosis in AML1/ETO-expressing cells only, pointing to AML1/ETO as a factor predisposing cells to hypoxia-induced apoptosis. In AML1/ETO-expressing cells, hypoxia enhanced TRAIL expression and its proapoptotic effects. AML1/ETO was found to bind TRAIL promoter and induce TRAIL transcription, although TRAIL expression was restrained by a concomitant relative transcription block. In hypoxia, such a TRAIL repression was removed and an increase of TRAIL expression was induced. Finally, blocking anti-TRAIL antibodies markedly reduced (Kasumi-1 cells) or completely inhibited (U937-A/E cells) hypoxia-induced apoptosis. Taken together, these results indicated that hypoxia induces apoptosis in AML1/ETO-expressing cells via a TRAIL/caspase 8-dependent autocrine loop and that TRAIL is a key regulator of hypoxia-induced apoptosis in these cells.

AML1/ETO sensitizes via TRAIL acute myeloid leukemia cells to the pro-apoptotic effects of hypoxia / Valentina Barbetti; Ignazia Tusa; Maria Grazia Cipolleschi; Elisabetta Rovida; Persio Dello Sbarba. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - ELETTRONICO. - 4:(2013), pp. e536-8. [10.1038/cddis.2013.49]

AML1/ETO sensitizes via TRAIL acute myeloid leukemia cells to the pro-apoptotic effects of hypoxia

BARBETTI, VALENTINA;TUSA, IGNAZIA;CIPOLLESCHI, MARIA GRAZIA;ROVIDA, ELISABETTA;DELLO SBARBA, PERSIO
2013

Abstract

We determined the effects of severe hypoxia (B0.1% O2) on acute myeloid leukemia cells expressing the AML1/ETO oncogene. Incubation of Kasumi-1 cells in hypoxia induced growth arrest, apoptosis and reduction of AML1/ETO protein expression. The conditional expression of AML1/ETO in U937-A/E cells showed that hypoxia induces marked apoptosis in AML1/ETO-expressing cells only, pointing to AML1/ETO as a factor predisposing cells to hypoxia-induced apoptosis. In AML1/ETO-expressing cells, hypoxia enhanced TRAIL expression and its proapoptotic effects. AML1/ETO was found to bind TRAIL promoter and induce TRAIL transcription, although TRAIL expression was restrained by a concomitant relative transcription block. In hypoxia, such a TRAIL repression was removed and an increase of TRAIL expression was induced. Finally, blocking anti-TRAIL antibodies markedly reduced (Kasumi-1 cells) or completely inhibited (U937-A/E cells) hypoxia-induced apoptosis. Taken together, these results indicated that hypoxia induces apoptosis in AML1/ETO-expressing cells via a TRAIL/caspase 8-dependent autocrine loop and that TRAIL is a key regulator of hypoxia-induced apoptosis in these cells.
2013
4
e536
8
Valentina Barbetti; Ignazia Tusa; Maria Grazia Cipolleschi; Elisabetta Rovida; Persio Dello Sbarba
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/803951
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