Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia

• Published in: Cancer gene therapy 2020-02, Vol.27 (1-2), p.15-21
• Main Authors: Cui, Longzhen, Cheng, Zhiheng, Liu, Yan, Dai, Yifeng, Pang, Yifan, Jiao, Yang, Ke, Xiaoyan, Cui, Wei, Zhang, Qingyi, Shi, Jinlong, Fu, Lin
• Format: Article
• Language: English
• Subjects: 631/337; 631/67/1990; Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Analysis; Apoptosis; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Bone Marrow - pathology; Cancer; Cell differentiation; Cell proliferation; Datasets as Topic; Dehydrogenases; Disease-Free Survival; Female; Gene Expression; Gene Expression Regulation, Leukemic; Gene Therapy; Genetic aspects; Genomes; Glycolysis; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Kaplan-Meier Estimate; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Male; Malignancy; Medical prognosis; Medical research; Medicine, Experimental; Middle Aged; Multivariate analysis; Myeloid cells; Myeloid leukemia; Prognosis; Pyruvate dehydrogenase (lipoamide); Pyruvate Dehydrogenase Acetyl-Transferring Kinase - analysis; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - genetics; Pyruvic acid; Risk factors; Stem cell transplantation; Transplantation; Transplantation, Homologous; Tumor cells; Young Adult
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-018-0071-9

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). 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.