Disruption of the Hippo pathway promotes the proliferation of childhood acute lymphoblastic leukemia cells, inhibits apoptosis and chemosensitivity.

Abstract

Background: Despite advancements in chemotherapy and stem cell transplantation, the recurrence and chemoresistance of childhood acute lymphoblastic leukemia (cALL) remain a significant challenge, thus indicating the need for novel therapeutic targets.

Research design and methods: The protein levels of YAP1, p-YAP1, TAZ, and Cyr61 of cALL patients and healthy volunteers were measured by western blot analysis. Then the leukemic cell line SUP-B15 was transfected with sh-YAP1 and pcDNA3.1-YAP1 to knockdown or overexpress YAP1. The viability, chemosensitivity, apoptosis, migration, and invasion of SUP-B15 cells were determined by MTT, flow cytometry, and Transwell assay.

Results: The cALL patients had higher YAP1, TAZ, and Cyr61 protein expression and lower p-YAP1 protein expression in bone marrow tissues compared with healthy volunteers (p < 0.01). In SUP-B15 cells, YAP1 knockdown upregulated p-YAP1 protein expression (p < 0.01) and downregulated TAZ and Cyr61 protein expression (p < 0.01). In addition, knocking down YAP1 significantly inhibited cell viability, migration, and invasion, and induced apoptosis (p < 0.01). YAP1 knockdown also reduced the IC₅₀ value following treatment with vincristine, daunorubicin, cyclophosphamide, and dexamethasone (p < 0.05).

Conclusions: Disruption of the Hippo pathway attenuates the development of cALL by promoting cell proliferation while suppressing apoptosis and drug sensitivity.