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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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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Cancer Gene Therapy (2019)