Telomere length and telomerase mutations in peripheral blood leukocytes of children with chronic aplastic anemia

WANG Xi-Ge; WANG Xuan; LIU Song; ZHOU Yu-Jie; WANG Dan-Feng

doi:10.7499/j.issn.1008-8830.2014.04.013

PDF(1624 KB)

Chinese Journal of Contemporary Pediatrics ›› 2014, Vol. 16 ›› Issue (4) : 375-379. DOI: 10.7499/j.issn.1008-8830.2014.04.013

CLINICAL RESEARCH

Telomere length and telomerase mutations in peripheral blood leukocytes of children with chronic aplastic anemia

WANG Xi-Ge¹, WANG Xuan¹, LIU Song², ZHOU Yu-Jie¹, WANG Dan-Feng³

Author information +

History +

Abstract

Objective To investigate the change in telomere length and TERC and TERT mutations in peripheral blood leukocytes of children with chronic aplastic anemia (CAA). Methods Sixty-nine children with CAA were divided into u ntreated group (n=24) who did not receive immunosuppressive therapy (IST), response group (n=36) who showed response to IST, and non-response group (n=9) who showed no response to IST; another 35 healthy children matched for age and sex were selected as the control group. The telomere-to-single copy gene (T/S) ratio in peripheral blood leukocytes was measured by real-time PCR in all groups. PCR was performed to detect TERC and TERT mutations in all children with CAA. Results The untreated and non-response groups had significantly lower T/S ratios than the control and response groups (P<0.01), whereas there was no significant difference in T/S ratio between the response and control groups (P>0.05). TERC and TERT mutations were not found in all children with CAA. Conclusions The change in telomere length in children with CAA may be related to the development and progression of disease. Telomere length measurement may be used as a prognostic indicator in children with CAA.

Key words

Aplastic anemia / Telomere / Telomerase / Mutation / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

WANG Xi-Ge, WANG Xuan, LIU Song, ZHOU Yu-Jie, WANG Dan-Feng. Telomere length and telomerase mutations in peripheral blood leukocytes of children with chronic aplastic anemia[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(4): 375-379 https://doi.org/10.7499/j.issn.1008-8830.2014.04.013

References

[1] Calado RT. Telomeres and marrow failure[J]. Hematology Am Soc Hematol Educ Program, 2009, 2009(1): 338-343.
[2] 王西阁, 周玉洁, 王丹凤, 等. 再生障碍性贫血患儿骨髓造血干细胞端粒酶活性及相关基因表达的研究[J]. 中国当代儿科杂志, 2013, 15(1): 25-28.
[3] 中国小儿血液与肿瘤杂志编辑委员会. 小儿再生障碍性贫血诊疗建议[J]. 中国小儿血液与肿瘤杂志, 2007, 12(5): 236-240.
[4] 郭令军, 张七一. 实时定量 PCR 分析外周血白细胞的端粒长度[J]. 中外医疗, 2008, 27 (21): 1-2.
[5] Gil ME, Coetzer TL. Real-time quantitative PCR of telomere length[J]. Mol biotechnol, 2004, 27(2): 169-172.
[6] Vulliamy T, Marrone A, Dokal I, et al. Association between aplastic anaemia and mutations in telomerase RNA[J]. Lancet, 2002, 359(9324): 2168-2170.
[7] Yamaguchi H, Calado RT, Ly H, et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia[J]. N Engl J Med, 2005, 352(14): 1413-1424.
[8] Georgin-Lavialle S, Aouba A, Mouthon L, et al. The telomere/telomerase system in autoimmune and systemic immune-mediated diseases[J]. Autoimmun Rev, 2010, 9(10): 646-651.
[9] Fleisig HB, Wong JMY. Telomerase as a clinical target:current strategies and potential applications[J]. Exp Gerontol, 2007, 42(1): 102-112.
[10] Scheinberg P, Cooper JN, Sloand EM, et al. Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia[J]. JAMA, 2010, 304(12): 1358-1364.
[11] Field JJ, Mason PJ, An P, et al. Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome[J]. J Pediatr Hematol Oncol, 2006, 28(7): 450-453.
[12] Liang J, Yagasaki H, Kamachi Y, et al. Mutations in telomerase catalytic protein in Japanese children with aplastic anemia[J]. Haematologica, 2006, 91(5): 656-658.
[13] 李英梅, 杨舟, 郑以州. 再生障碍性贫血造血干/祖细胞缺陷新认识[J]. 国际输血及血液学杂志, 2008, 31(1): 29-32.
[14] Zhao YM, Li JY, Lan JP, et al. Cell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells[J]. Biochem Biophys Res Commun, 2008, 369(4): 1114-1119.
[15] Bekaert S, De Meyer T, Rietzschel ER, et al. Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease[J]. Aging cell, 2007, 6(5): 639-647.
[16] 赵芬英, 徐晓军, 宋华, 等. 儿童再生障碍性贫血免疫抑制剂治疗疗效及相关因素分析[J]. 中国当代儿科杂志, 2012, 14(8): 567-570.
[17] 葛美丽, 郑以州. 再生障碍性贫血造血干/祖细胞克隆性演变的病理生理机制研究现状[J]. 中华血液学杂志, 2010, 31(11): 784-786.
[18] Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia[J]. Blood, 2006, 108(8): 2509-2519.