Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia
Authors Gao L, Sun J, Liu F, Zhang H, Ma Y
Received 27 August 2015
Accepted for publication 31 December 2015
Published 9 February 2016 Volume 2016:9 Pages 711—722
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Chiung-Kuei Huang
Peer reviewer comments 3
Editor who approved publication: Professor Daniele Santini
Li Gao,1,* Junzhong Sun,2,* Fang Liu,2,3,* Hui Zhang,1 Yigai Ma1
1Department of Hematology, China–Japan Friendship Hospital, 2Department of Hematology and Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, 3Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China
*These authors contributed equally to this work
Background: Although the biological insight of acute myeloid leukemia (AML) has increased in the past few years, the discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Systematical studies concerning the clinical implications and genetic correlations of HOXA9 aberrations in patients with AML are relatively promising.
Materials and methods: Here, we investigated mutational status and the mRNA levels of the HOXA9 gene in 258 patients with AML. Furthermore, hematological characteristics, chromosome abnormalities, and genetic mutations associated with AML were analyzed, followed by the assessment of clinical survival. Besides, the expression level and mutational status of MEIS1, a cofactor of HOXA9, were also detected in patients with AML with the aim of a deeper understanding about the homeodomain-containing transcription factors associated with hematological characteristics.
Results: HOXA9 and MEIS1 mutations were detected in 4.26% and 3.49% AML cases, respectively. No correlations were detected between mutation status and clinical characteristics, cytogenetic and genetic aberrations, and clinical survival. Higher HOXA9 expression levels were correlated with white blood cell count and closely associated with unfavorable karyotype as well as MLL-PTD and EZH2 mutations, whereas, there was an inverse correlation with the French–American–British M3 subtype. Compared with patients with lower HOXA9 expression levels, those with higher HOXA9 expression levels had a lower complete remission rate and inferior survivals in both AML and cytogenetically normal AML.
Conclusion: HOXA9 expression may serve as a promising biomarker to ameliorate a prognostic model for predicting clinical outcome and consummating individualized treatment in patients with AML.
Keywords: acute myeloid leukemia, HOXA9, expression, clinical survival
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]