PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia

PRICKLE1 是一种 Wnt/PCP 信号成分,在急性髓系白血病中过度表达并与预后不良相关

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作者:Duanfeng Jiang, Yanjuan He, Qiuyu Mo, Enyi Liu, Xin Li, Lihua Huang, Qin Zhang, Fangping Chen, Yan Li, Haigang Shao

Background

Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) remains unknown. This study aims to characterize the prognostic significance of PRICKLE1 expression in patients with AML.

Conclusions

These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML.

Methods

RNA-seq was performed to compare mRNA expression profiles of AML patients and healthy controls. qRT-PCR and western blotting were used to analyze the expression of PRICKLE1 in AML patients and cell lines, and two independent datasets (TCGA-LAML and TARGET-AML) online were used to validate the expression

Results

Our data showed that PRICKLE1 expression levels were markedly high in AML patients at the time of diagnosis, decreased after complete remission and increased again at relapse. Of note, PRICKLE1 was highly expressed in drug resistant AML cells and monocytic-AML patients. High PRICKLE1 expression was found in FLT3/DNMT3A/IDH1/IDH2-mutant AML and associated with poor prognosis. Furthermore, high expression of PRICKLE1 may be correlated with migration and invasion components upregulation in AML patients. Conclusions: These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML.

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