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

Cancer Gene Therapy volume 27, pages 15–21 (2020)Cite this article

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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.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81500118, 61501519), the China Postdoctoral Science Foundation funded project (Project No.2016M600443), Jiangsu Province Postdoctoral Science Foundation funded project (Project No.1701184B).

Author information

Author notes

  1. These authors contributed equally: Longzhen Cui, Zhiheng Cheng

  2. These authors jointly supervised the study: Wei Cui, Qingyi Zhang, Jinlong Shi, Lin Fu.

Authors and Affiliations

  1. Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Longzhen Cui, Zhiheng Cheng, Yan Liu, Jinlong Shi & Lin Fu

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

    Longzhen Cui & Lin Fu

  3. Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China

    Longzhen Cui, Xiaoyan Ke & Lin Fu

  4. Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, 515041, China

    Zhiheng Cheng & Yifeng Dai

  5. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands

    Yifeng Dai

  6. Department of Medicine, William Beaumont Hospital, Royal Oak, MI, 48073, USA

    Yifan Pang

  7. Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, 310058, China

    Yang Jiao

  8. Department of Clinical Laboratory, Beijing Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, 100080, China

    Wei Cui

  9. Department of Hematology of Air Force PLA General Hospital, Beijing, China

    Qingyi Zhang

  10. Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, 100853, China

    Jinlong Shi

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  1. Longzhen Cui
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Correspondence to Lin Fu.

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Cui, L., Cheng, Z., Liu, Y. et al. Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia. Cancer Gene Ther 27, 15–21 (2020). https://doi.org/10.1038/s41417-018-0071-9

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