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Human MutT homologue 1 mRNA overexpression correlates to poor response of multiple myeloma

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Abstract

Human MutT homologue 1 (MTH1) is a human 8-oxo-dGTPase that eradicates oxidized bases in the nucleotide pool and DNA. MTH1 is critical for RAS-transformed cancer cell survival, whereas it is dispensable in normal cells and tissues. Here, we determined the expression of MTH1 in multiple myeloma (MM) cell lines and MM patients’ CD138 (+) cells and analyzed its potential clinical significance. We detected overexpression of MTH1 mRNA in three cell lines (RPMI 8226, U266, and H929). MTH1 mRNA expression of RPMI8226 was higher than that of U266 and H929. In 59 MM patients, overexpression of MTH1 mRNA was detected in 27 cases (45.7%). MTH1 mRNA expression was significantly higher in ISS III stage (P < 0.001) and refractory relapse patients (P < 0.05). MTH1 mRNA expression in patients achieving less than partial response (PR) was significantly higher than in those achieving PR and better in newly diagnosed MM (P = 0.04). In conclusion, higher MTH1 may be associated with later disease stage and advanced disease progression. MTH1 mRNA overexpression is also correlated poor efficacy of bortezomib in newly diagnosed MM patients.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (General Program, Grant No. 81172252) and the Capital of Clinical Characteristics and the Applied Research Fund of China (Grant No. Z131107002213146).

The authors gratefully acknowledge the co-investigators who participated in this study. The corresponding author Wenming Chen designed the research study and reviewed the paper. Huixing Zhou performed the research and wrote the paper. Huixing Zhou and Yuan Jian analyzed the data. Yun Leng, Nian Liu, Ying Tian, Guorong Wang, Guangzhong Yang, and Wen Gao contributed essential patients’ samples collection and reagents.

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  1. Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongti South Road, Beijing, 100020, People’s Republic of China

    Huixing Zhou, Yuan Jian, Yun Leng, Nian Liu, Ying Tian, Guorong Wang, Wen Gao, Guangzhong Yang & Wenming Chen

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  1. Huixing Zhou
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12185_2016_2139_MOESM1_ESM.tif

Supplementary Fig. 1 MTH1 mRNA expression in patients’ CD138(-) cells and normal mononuclear cells (P > 0.05) (TIFF 56 kb)

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Zhou, H., Jian, Y., Leng, Y. et al. Human MutT homologue 1 mRNA overexpression correlates to poor response of multiple myeloma. Int J Hematol 105, 318–325 (2017). https://doi.org/10.1007/s12185-016-2139-3

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  • DOI: https://doi.org/10.1007/s12185-016-2139-3

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