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PAK 家族激酶在急性髓系白血病中的预后意义。

Prognostic significance of PAK family kinases in acute myeloid leukemia.

机构信息

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

出版信息

Cancer Gene Ther. 2020 Feb;27(1-2):30-37. doi: 10.1038/s41417-019-0090-1. Epub 2019 Mar 20.

Abstract

Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by a myriad of genetic defects. Genetic abnormalities are powerful prognostic factors. P21-activated kinases (PAKs) are a kind of serine/threonine protein kinases, which is regulator of plenty of oncogenic signaling pathways. The clinical and prognostic value of PAKs in AML is unclear. A total of 155 AML patients with PAK expression data from The Cancer Genome Atlas database were enrolled in this study. Eighty-four patients underwent chemotherapy only, 71 also underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the chemotherapy-only group, high PAK3 and PAK7 expression were both bound up with poor EFS and OS (all P < 0.05). However, high PAK2 expressers had better EFS and OS (all P < 0.05). Multivariate analysis demonstrated that high PAK7 expression was an adverse independent prognostic factor in patients who received chemotherapy only. PAKs have no influence in EFS and OS in patients who underwent allo-HSCT. In conclusion, high PAK2 expression is a favorable prognostic factor, as to the high expression of PAK3 and PAK7, they are poor prognostic factors, and PAK7 has better prognostic value, but their prognostic effects can be offset by allo-HSCT.

摘要

急性髓系白血病(AML)是一种克隆性和异质性疾病,其特征是存在多种遗传缺陷。遗传异常是强有力的预后因素。P21 激活激酶(PAKs)是一种丝氨酸/苏氨酸蛋白激酶,是许多致癌信号通路的调节剂。PAKs 在 AML 中的临床和预后价值尚不清楚。本研究共纳入了来自癌症基因组图谱数据库的 155 例 AML 患者的 PAK 表达数据。其中 84 例仅接受化疗,71 例同时接受异基因造血干细胞移植(allo-HSCT)。在仅接受化疗的患者中,高 PAK3 和 PAK7 表达均与不良 EFS 和 OS 相关(均 P<0.05)。然而,高 PAK2 表达者具有更好的 EFS 和 OS(均 P<0.05)。多因素分析表明,在仅接受化疗的患者中,高 PAK7 表达是不良的独立预后因素。在接受 allo-HSCT 的患者中,PAKs 对 EFS 和 OS 没有影响。总之,高 PAK2 表达是一个有利的预后因素,而高 PAK3 和 PAK7 表达则是不良的预后因素,PAK7 具有更好的预后价值,但它们的预后作用可以被 allo-HSCT 抵消。

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