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

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...

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Bibliographic Details
Published in:Oncotarget 2017-09, Vol.8 (42), p.72250-72259
Main Authors: Lee, Sze-Hwei, Chiu, Yu-Chiao, Li, Yi-Hung, Lin, Chien-Chin, Hou, Hsin-An, Chou, Wen-Chien, Tien, Hwei-Fang
Format: Article
Language:English
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Research Paper
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Summary: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 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 since it was the only one in DOCK family to be associated with survival. Physiological functions and biological pathways associated with were identified using bioinformatics approaches. With a median follow up of 57 months, higher expression was associated with shorter disease free and overall survival. The finding could be validated by two independent cohorts. Multivariate analysis showed higher expression as a strong independent unfavorable prognostic factor. Higher expression was closely associated with older age, higher platelet and peripheral blast counts, intermediate-risk cytogenetics, -ITD, -PTD and mutations in , , , and . Functional enrichment analysis suggested the association of overexpression with several key physiological pathways including cell proliferation, motility, and chemotaxis. Therefore, we suggested that AML with higher expression showed characteristic clinical and biological features. 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 in the leukemogenesis are warranted.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.19706