Oncotarget

Research Papers:

High expression of dedicator of cytokinesis 1 (DOCK1) confers poor prognosis in acute myeloid leukemia

Sze-Hwei Lee, Yu-Chiao Chiu, Yi-Hung Li, Chien-Chin Lin, Hsin-An Hou, Wen-Chien Chou _ and Hwei-Fang Tien

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Oncotarget. 2017; 8:72250-72259. https://doi.org/10.18632/oncotarget.19706

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Abstract

Sze-Hwei Lee1,*, Yu-Chiao Chiu2,*, Yi-Hung Li1, Chien-Chin Lin1,3, Hsin-An Hou1, Wen-Chien Chou1,3 and Hwei-Fang Tien1

1Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Wen-Chien Chou, email: [email protected]

Hwei-Fang Tien, email: [email protected]

Keywords: DOCK1, acute myeloid leukemia, prognosis, stemness, cell migration

Received: April 25, 2017     Accepted: June 29, 2017     Published: July 31, 2017

ABSTRACT

DOCK family genes encode evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase involving multiple biological functions. Yet the patterns and prognostic significance of their expression in acute myeloid leukemia (AML) remain unexplored. Here we analyzed the expression patterns of 11 DOCK family genes in AML cells based on the array data of 347 patients from our cohort and several other published datasets. We further focused on the implications of the expression of DOCK1 since it was the only one in DOCK family to be associated with survival. Physiological functions and biological pathways associated with DOCK1 were identified using bioinformatics approaches. With a median follow up of 57 months, higher DOCK1 expression was associated with shorter disease free and overall survival. The finding could be validated by two independent cohorts. Multivariate analysis showed higher DOCK1 expression as a strong independent unfavorable prognostic factor. Higher DOCK1 expression was closely associated with older age, higher platelet and peripheral blast counts, intermediate-risk cytogenetics, FLT3-ITD, MLL-PTD and mutations in PTPN11, NPM1, RUNX1, ASXL1 and DNMT3A. Functional enrichment analysis suggested the association of DOCK1 overexpression with several key physiological pathways including cell proliferation, motility, and chemotaxis. Therefore, we suggested that AML with higher DOCK1 expression showed characteristic clinical and biological features. DOCK1 expression is an important prognostic marker and a potential therapeutic target for the treatment of AML. Studies in large prospective cohorts are necessary to confirm our findings. Further mechanistic studies to delineate the role of DOCK1 in the leukemogenesis are warranted.


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