Association analysis of the expression level of Nrf2 mRNA in peripheral blood nucleated cells and the severity of chemotherapy-induced myelosuppression

Qingshan Wang, Lingling Li, Yu Chen, Sen Liu, Mingde Yin


Objective: To investigate the interindividual variation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression level in the peripheral blood nucleated cells and its correlation with the severity of chemotherapy-induced myelosuppression. Methods: The expression level of Nrf2 mRNA in the peripheral blood nucleated cells from 30 cases of cancer was detected by semi-quantitative RT-PCR before chemotherapy, and the association between the Nrf2 mRNA expression and the chemotherapy-induced myelosuppression was analyzed. Results: The Nrf2 mRNA expression level in the peripheral blood mononuclear cells exhibited significant interindividual differences. The Nrf2 mRNA expression level was significantly higher in the patients with grades 0-1 leukopenia or neutropenia than that in the patients with grades 2-4 (P<0.05), but it was not associated with the age, gender, chemotherapeutic regimen and the type of tumor. The association analysis showed that the Nrf2 mRNA expression level in the peripheral blood mononuclear cells was negatively associated with leukopenia and neutropenia (r = –0.448, P = 0.013; r = –0.493, P = 0.006). Conclusion: The expression level of Nrf2 mRNA in the peripheral blood mononuclear cells is significantly correlated with chemotherapy-induced myelosuppression. It may be employed as an ideal marker to predict the severity of chemotherapy-induced myelosuppression and helpful for clinical decision-making and early prevention and treatment of myelosuppression.


neoplasms; antineoplastic combined chemotherapy protocols; leukopenia; neutropenia; nuclear factor erythroid-2-related factor 2

Full Text:



National Cancer Prevention and Cure Research Office, The National Cancer Registration Center, The Ministry of health and prevention and Control Bureau compiling the death from cancer report in China——The third National Death retrospective sampling survey[M]. Beijing: People's Medical Publishing House , 2010.

FRIBERG L E, KARLSSON M O. Mechanistic models for myelosuppression[J]. Invest New Drugs, 2003,21(2):183–194.

CANCELAS J A, KOEVOET W L, DE KONING A E,et al. Connexin-43 gap junctions are involved in multiconnexin-expressing stromal support of hemopoietic progenitors and stem cells[J]. Blood,2000, 96(2):498–505.

ITO K, HIRAO A, ARAI F, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells[J]. Nat Med, 2006, 12(4):446−451.

NUMAZAWA S, SUGIHARA K, MIYAKE S, et al. Possible involvement of oxidative stress in 5-fluorouracil-mediated myelosuppression in mice[J]. Basic Clin Pharmacol Toxicol, 2011, 108 (1):40-45.

YU S, KONG A N. Targeting carcinogen metabolism by dietary cancer preventive compounds [J]. Curr Cancer Drug Targets, 2007, 7(5):416-424.

JUNG KA, KWAK M K. The Nrf2 system as a potential target for the development of indirect antioxidants[J]. Molecules, 2010,15(10):7266-7291.

NIH, NCI. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAEv3 )[EB/OL] Bethesda, Maryland 20892, Public Health Service, National Institutes of Health, National Cancer Institute, 2003 [2006 -08-19]. docs/ctcaev3.pdf

LYMAN G H, LYMAN C H, AGBOOLA O. Risk models for predicting chemotherapy-induced neutropenia[J]. Oncologist, 2005, 10(6):427-437.

Guo Yan Xia , Yu Cheng Bao , Liu Qiu Ju . Establishment of predictive model for myelosuppression after chemotherapy[J]. Jilin Medical Journal, 2005, (12):1257-1259.

Cai Xun ,Xue Peng , Song Wei Feng , etc . Role of serum concentration monitoring of fluorouracil in further improving chemotherapy efficacy and reducing adverse reactions in advanced gastric cancer [J]. Tumor , 2011, 31(10): 930-036.

HOSSEINIMEHR S J, KARAMI M. Chemoprotective effects of captopril against cyclophosphamideinduced genotoxicity in mouse bone marrow cells[J]. Arch Toxicol, 2005, 79(8): 482–486.

KATO K, TAKAHASHI K, MONZEN S, et al . Relationship between radiosensitivity and Nrf2 target gene expression in human hematopoietic stem cells[J]. Radiat Res, 2010, 174(2):177-184.

FRIEDMAN A D. Transcriptional control of granulocyte and monocyte development[J]. Oncogene, 2007, 26(47):6816–6828.

GORDON S, TAYLOR P R. Monocyte and macrophage heterogeneity[J]. Nat Rev Immunol,2005, 5(12):953–964.

MOTOHASHI H, YAMAMOTO M. Carcinogenesis and transcriptional regulation through Maf recognition elements[J]. Cancer Sci, 2007, 98(2):135-139.

QUE L L, WANG H X, CAO B S, et al. The regulation and functions of transcription factor Nrf2 in cancer chemoprevention and chemoresistance[J]. J Chin Pharm Sci, 2011, 20(1):5-19.



  • There are currently no refbacks.

Copyright (c) 2018 Qingshan Wang, Lingling Li, Yu Chen, Sen Liu, Mingde Yin

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.