HIF-1α forms regulatory loop with YAP to coordinate hypoxia-induced adriamycin resistance in acute myeloid leukemia cells.

Despite improvement in Acute Myeloid Leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemo-resistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found AML cells showed less susceptibility to ADR in the presence of hypoxia, while inhibition of HIF-1α by CdCl2 can make AML cells re-susceptibility to ADR even under hypoxia. Moreover, HIF-1α is overexpressed and plays important role in ADR resistant maintenance in resistant AML cells. We further found Hypoxia or induction of HIF-1α can significantly up-regulate YAP expression in AML cells, and resistant cells express high level of YAP. Finally, we found that YAP may not only enhance HIF-1α stability, but promote HIF-1α's activity on target gene PKM2. In conclusion, Our data indicate HIF-1α or YAP may represent a therapeutic target for overcoming resistance to adriamycin-based chemotherapy in AML. This article is protected by copyright. All rights reserved.