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

Longzhen Cui, Zhiheng Cheng, Yan Liu, Yifeng Dai, Yifan Pang, Yang Jiao, Xiaoyan Ke, Wei Cui, Qingyi Zhang, Jinlong Shi, Lin Fu*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    33 Citations (Scopus)
    85 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)15-21
    Number of pages7
    JournalCancer Gene Therapy
    Volume27
    Issue number1-2
    DOIs
    Publication statusPublished - Feb-2020

    Keywords

    • PYRUVATE-DEHYDROGENASE
    • FAVORABLE PROGNOSIS
    • CEBPA MUTATIONS
    • KINASE
    • CANCER
    • HYPOXIA
    • METABOLISM
    • SURVIVAL
    • PKC
    • AML

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