Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China.
Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
Cancer Gene Ther. 2020 Feb;27(1-2):15-21. doi: 10.1038/s41417-018-0071-9. Epub 2018 Dec 22.
Acute myeloid leukemia (AML) is a hematological malignancy characterized by the proliferation of immature myeloid cells, with impaired differentiation and maturation. Pyruvate dehydrogenase kinase (PDK) is a pyruvate dehydrogenase complex (PDC) phosphatase inhibitor that enhances cell glycolysis and facilitates tumor cell proliferation. Inhibition of its activity can induce apoptosis of tumor cells. Currently, little is known about the role of PDKs in AML. Therefore, we screened The Cancer Genome Atlas (TCGA) database for de novo AML patients with complete clinical information and PDK family expression data, and 84 patients were included for the study. These patients did not undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Univariate analysis showed that high expression of PDK2 was associated with shorter EFS (P = 0.047), and high expression of PDK3 was associated with shorter OS (P = 0.026). In multivariate analysis, high expression of PDK3 was an independent risk factor for EFS and OS (P < 0.05). In another TCGA cohort of AML patients who underwent allo-HSCT (n = 71), PDK expression was not associated with OS (all P > 0.05). Our results indicated that high expressions of PDK2 and PDK3, especially the latter, were poor prognostic factors of AML, and the effect could be overcome by allo-HSCT.
急性髓系白血病(AML)是一种血液系统恶性肿瘤,其特征是不成熟髓样细胞的增殖,伴有分化和成熟受损。丙酮酸脱氢酶激酶(PDK)是丙酮酸脱氢酶复合物(PDC)磷酸酶抑制剂,可增强细胞糖酵解并促进肿瘤细胞增殖。抑制其活性可诱导肿瘤细胞凋亡。目前,关于 PDKs 在 AML 中的作用知之甚少。因此,我们筛选了包含完整临床信息和 PDK 家族表达数据的癌症基因组图谱(TCGA)数据库中的初诊 AML 患者,共有 84 例患者纳入研究。这些患者未接受异基因造血干细胞移植(allo-HSCT)。单因素分析显示,PDK2 高表达与较短的 EFS(P=0.047)相关,PDK3 高表达与较短的 OS(P=0.026)相关。多因素分析显示,PDK3 高表达是 EFS 和 OS 的独立危险因素(P<0.05)。在接受 allo-HSCT 的另一 TCGA AML 患者队列(n=71)中,PDK 表达与 OS 无关(均 P>0.05)。我们的研究结果表明,PDK2 和 PDK3 的高表达,特别是后者,是 AML 的不良预后因素,allo-HSCT 可克服这种影响。