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.

KEYWORDS:

• Childhood acute lymphoblastic leukemia
• Hippo pathway
• chemosensitivity
• proliferation
• apoptosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

H Jiang designed the study. RB Zhang, J Peng, and L Ren collated the data, carried out data analyses, and produced the initial draft of the manuscript. HD Wang contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Ethical approval

This study was approved by the Ethics Committee of Taihe Hospital, Hubei University of Medicine, China. Written informed consent was obtained from all participants.

Data availability statement

Datasets used in this article are available from the corresponding author on reasonable request.

Additional information

Funding

This paper was not funded.