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Aberrant histone modification in CD19+ B cells of the patients with chronic lymphocytic leukemia

Authors Zhou K, Zhang Q, Liu Y, Xiong Y, Wu S, Yang J, Zhou H, Liu X, Wei X, Song Y

Received 2 September 2016

Accepted for publication 9 December 2016

Published 23 February 2017 Volume 2017:10 Pages 1173—1179

DOI https://doi.org/10.2147/OTT.S121301

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr William Cho

Keshu Zhou, Qing Zhang, Yanyan Liu, Yuanyuan Xiong, Shengsheng Wu, Jingke Yang, Hu Zhou, Xinjian Liu, Xudong Wei, Yongping Song

Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China

Abstract: The aim of this study was to detect the alterations in histone methylation and acetylation in patients with chronic lymphocytic leukemia (CLL). Global histone H3/H4 acetylation and H3K4/H3K9 methylation were detected by the EpiQuik™ global histone H3/H4 acetylation and H3K4/H3K9 methylation assay kits. The mRNA expression of selected chromatin modifier genes was measured by real-time polymerase chain reaction (RT-PCR). Our results found that the global histone H3/H4 hypoacetylation in the CD19+ B cells of patients with CLL (P=0.028 and P=0.03, respectively) and the global histone H3K9 methylation in patients with CLL were significantly increased compared with controls (P=0.02), while there was no significant difference in the global histone H3K4 methylation between the two groups. The level of SIRT1 and EZH2 mRNA expression was upregulated in patients with CLL (P=0.03 and P=0.02, respectively), which increased significantly with progression from Binet stage A to stage C (P=0.015 and P=0.01, respectively) and Rai good to high risk stage (P=0.007 and P=0.008, respectively). The level of HDAC1 and HDAC7 mRNA expression was significantly increased (P=0.02 and P=0.008, respectively) and HDAC2 and P300 mRNA expression was reduced in patients with CLL (P=0.002 and P=0.001, respectively). In conclusion, it is observed that the aberrant histone modification plays an important role in the pathogenesis of CLL.

Keywords: histone methylation, histone acetylation, SIRT1, EZH2, CLL

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