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Prognostic role of DOK family adapters in acute myeloid leukemia

Cancer Gene Therapy volume 26, pages 305–312 (2019)Cite this article

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Abstract

Acute myeloid leukemia (AML) is a genetically and clinically heterogeneous disease. Gene mutational and expressional profile can aid the identification of different prognostic subgroups. Downstream of tyrosine kinase (DOK) proteins are a multigenic family of adaptors; some of them are key negative regulators of immune cell signaling. However, the expression and clinical implication of DOK family in AML has rarely been investigated. A total of 155 AML patients with DOK family (DOK1-7) expression data from The Cancer Genome Atlas database were enrolled in the study. In patients who only received chemotherapy, those with high expressions of DOK4 or DOK5 had significantly shorter EFS and OS than patients with low expressions (all P < 0.001), whereas high DOK7 expressers had longer EFS and OS than the low expressers (all P < 0.05). In patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, all DOK members had no impact on EFS and OS. Multivariate analysis confirmed that high DOK5 expression was an independent risk factor for EFS and OS in untransplanted patients (all P < 0.05). Our study suggests that in AML, high expressions of DOK4 and DOK5 are adverse prognostic factors, high DOK7 expression is a good prognostic factor, but their effects can 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), PLAGH project of Medical Big Data (Project No. 2016MBD-025).

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Author notes

  1. These authors contributed equally: Lin Zhang, Ran Li, Kai Hu, Yifeng Dai.

  2. These authors jointly supervised this work: Jinlong Shi, Zhiheng Cheng, Lin Fu.

Authors and Affiliations

  1. Department of Human Resources, Huaihe Hospital of Henan University, 475000, Kaifeng, China

    Lin Zhang

  2. Department of Surgery, Huaihe Hospital of Henan University, 475000, Kaifeng, China

    Ran Li

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

    Kai Hu & Lin Fu

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

    Yifeng Dai & Zhiheng Cheng

  5. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The 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, 310058, Hangzhou, China

    Yang Jiao

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

    Yan Liu, Longzhen Cui, Jinlong Shi & Zhiheng Cheng

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

    Jinlong Shi

  10. Department of Hematology, Huaihe Hospital of Henan University, 475000, Kaifeng, China

    Lin Fu

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  1. Lin Zhang
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Correspondence to Zhiheng Cheng or Lin Fu.

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Zhang, L., Li, R., Hu, K. et al. Prognostic role of DOK family adapters in acute myeloid leukemia. Cancer Gene Ther 26, 305–312 (2019). https://doi.org/10.1038/s41417-018-0052-z

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