Research on correlation of bone marrow CD4+CD25highFoxp3+ regulatory T cells with childhood acute B lymphoblastic leukemia

Abstract

Abstract: Objective　To analyze the forkhead box protein 3（Foxp3） mRNA expression and the CD4+ regulatory T cells（Treg） frequency in the bone marrow of childhood acute B lymphoblastic leukemia（B-ALL），and to investigate the relationship between Treg and the development and prognosis of childhood B-ALL. Methods　The levels of Foxp3 mRNA were detected in 35 children with B-ALL，68 patients with remission and 10 healthy controls by real-time polymerase chain reaction（PCR）. The CD4⁺ CD25^highFoxp3⁺ Treg were identified by flow cytometry. The interleukin-10（IL-10） expression level in bone marrow was detected by enzyme-linked immunosorbent assay（ELISA）. Results　The level of Foxp3 mRNA expression in B-ALL group was 4.44 times higher than that of control group. In minimal residual disease（MRD） positive group，it was 2.39 times higher than that in MRD negative group. The percentage median（M） of Treg in CD4+T cells was 12.77% in B-ALL group，which was significantly higher than that in control group（8.09%，P＜0.01）. In addition，Treg frequency in MRD positive group（M＝14.74%） was significantly different from that in MRD continuously negative group（M＝11.30%，P＜0.05）．The level of IL-10 in MRD positive group was（24.69±11.73）pg/mL，which was higher than that of MRD continuously negative group[（9.19±5.82）pg/mL，P＜0.05]. Conclusions　The frequency of Treg and Foxp3 mRNA are significantly elevated in patients with childhood B-ALL and patients with positive MRD，and the IL-10 level in bone marrow is consistent with the frequency of Treg. Treg can be used to evaluate the prognosis and relapse of childhood B-ALL，and may play its role by secreting inhibitory cytokine IL-10.

Key words: Regulatory T cell, Forkhead box protein 3, Acute B lymphoblastic leukemia, Minimal residual disease

JIANG Limin;XU Chong;FU Qihua . Research on correlation of bone marrow CD4⁺CD25^highFoxp3⁺ regulatory T cells with childhood acute B lymphoblastic leukemia[J]. , 2012, 27(7): 601-605.

References

[1]Beyer M，Schultze JL. Regulatory T cells in cancer[J]. Blood，2006，108（3）：804-811.
[2]李爱华，邱国强，顾伟英，等. CD4+CD25+ Treg在急性淋巴细胞白血病患者外周血中的表达及其体外实验研究[J]. 细胞与分子免疫学杂志，2007，23（5）：439-442.
[3]Curti A，Trabanelli S，Onofri C，et al. Indoleamine 2，3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells[J]. Haema-tologica，2010，95（12）：2022-2030.
[4]Curti A，Pandolfi S，Valzasina B，et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells[J]. Blood，2007，109（7）： 2871-2877.
[5]殷君慧．小儿急性白血病化学治疗[M]. 北京：科学出版社，1997：47.
[6]Bach JF. Regulatory T cells under scrutiny[J]. Nat Rev Immunol，2003，3（3）：189-198.
[7]Ziegler SF. FOXP3：of mice and men[J]. Annu Rev Immunol，2006，24：209-226.
[8]Hinz S，Pagerols-Raluy L，Oberg HH，et al. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer[J]. Cancer Res，2007，67（17）：8344-8350.
[9]Clark FJ，Gregg R，Piper K，et al. Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25 high regulatory T cells[J]. Blood，2004，103（6）：2410-2416.
[10]Stockis J，Fink W，Francois V，et al. Comparison of stable human Treg and Th clones by transcriptional profiling[J]. Eur J Immunol，2009，39（3）：869-882.
[11]Zou W. Regulatory T cells，tumour immunity and immunotherapy[J]. Nat Rev Immunol，2006，6（4）：295-307.
[12]Borsellino G，Kleinewietfeld M，Di Mitri D，et al. Expression of ectonucleotidase CD39 by Foxp3+Treg cells： hydrolysis of extracellular ATP and immune suppression[J]. Blood，2007，110（4）：1225-1232.
[13]Deaglio S，Dwyer KM，Gao W，et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression[J]. J Exp Med，2007，204（6）： 1257-1265.

Research on correlation of bone marrow CD4⁺CD25^highFoxp3⁺ regulatory T cells with childhood acute B lymphoblastic leukemia

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 9

Recommended Articles

Metrics

[1]	LIU Junshan, GUO Mingfa, SUN Jia, SHI Lihuan, LIU Wei, DUAN Yongtao. Significance of minimal residual disease dynamic monitoring in the prognosis of acute B-lymphoblastic leukemia children with positive and negative ETV6/RUNX1 fusion genes [J]. Laboratory Medicine, 2023, 38(3): 209-214.
[2]	ZOU Guanghui, SUN Fenyong, DAI Jiaqi, YAN Jie, ZHANG Yun, YIN Zhiqiang. Role of follicular regulatory T cells in the pathogenesis of Hashimoto thyroiditis [J]. Laboratory Medicine, 2019, 34(8): 682-686.
[3]	ZHAO Lian, HE Jinlong, WU Cuiyun, ZHOU Haiyan, ZHOU Weilun, WU Cuiping. Role of peripheral blood CD4⁺CD25^highTreg percentage in the prognosis of ALL [J]. Laboratory Medicine, 2019, 34(4): 327-330.
[4]	KE Xing, ZHANG Liang, SHEN Lisong. Preliminary study on the mechanism of CD4⁺CD25^highCD127^low regulatory T cells promoting the metastasis of epithelial ovarian cancer [J]. Laboratory Medicine, 2019, 34(2): 110-115.
[5]	ZHONG Jiaying, WU Yingying, LAO Mengxiao, ZHANG Xiaoyan, WANG Chunli, PAN Jianhua. Expressions of CD123 and CD66c in childhood B-cell acute lymphoblastic leukemia and their roles in monitoring minimal residual disease [J]. Laboratory Medicine, 2018, 33(9): 807-810.
[6]	XU Xinxin, WANG Yungang, CAI Hua, SHEN Pei, CHU Fuying. Influence of three dimensional conformal radiation therapy combined with chemotherapy on Treg in peripheral blood of esophagus carcinoma patients [J]. Laboratory Medicine, 2017, 32(5): 390-393.
[7]	YANG Tingting, WANG Qing, LI Zhi, PIAO Jun, PIAO Jing'ai. Study on Th17, Treg cell and the expression of relative cytokines in psoriasis patients [J]. Laboratory Medicine, 2015, 30(7): 715-719.
[8]	HU Yueming, MA Li, LI Hong.. The detections of peripheral blood Th17 cells and Treg cells in HBV infected patients and their significance [J]. , 2014, 29(1): 21-25.
[9]	QING Keqin,YANG Chaoguo,LIU Rong. Analysis on the change of CD4^＋CD25^＋Foxp3^＋ regulatory T cells in peripheral blood of patients with chronic hepatitis B [J]. , 2013, 28(9): 811-814.