LAUSR

BACKGROUND Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML). METHODS In this study, we established two ADM-resistant cell lines (THP-1/ ADM and K562/ ADM). Then cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real time PCR were performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot. RESULTS We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM-resistance, evidenced by the increased expression in ADM-resistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding this role of YAP1 regulates AML resistance by affecting CSCs characteristics. CONCLUSION In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM-resistance in AML. YAP1 might be novel biomarkers for treatment of drug-resistance in AML.