端粒酶基因突变与再生障碍性贫血_West China Medical Journal

Authors：

杨程蓉 ,  刘霆

Corresponding author：

刘霆, Email: ycr314558@163.com

Keywords：

再生障碍性贫血; 端粒; 端粒酶; 端粒酶基因突变; 雄激素

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近年来，端粒酶基因突变引起的端粒酶活性降低和端粒缩短，成为再生障碍性贫血（再障）发病机制的研究热点之一。大多数获得性再障患者是由免疫异常引起的，对免疫抑制治疗有效。约1/3的再障患者存在端粒缩短、端粒酶活性降低的情况，他们对免疫抑制剂治疗通常无效，而对雄激素治疗有效。雄激素在人体内可以通过芳香化转化为雌激素，与端粒酶基因启动子上的雌激素受体成分相结合而发生作用，从而增加端粒酶活性，恢复骨髓造血和外周血细胞数，彰显出治疗再障的作用。端粒酶基因突变和端粒酶活性异常是现今又一被肯定的再障发病机制，为临床治疗再障开辟了新的思路。

Citation： 杨程蓉,刘霆. 端粒酶基因突变与再生障碍性贫血. West China Medical Journal, 2012, 27(7): 1112-1114. doi: Copy

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14.	Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita[J]. Nature, 1999, 402(6761): 551-555.
15.	Ball SE, Gibson FM, Rizzo S, et al. Progressive telomere shortening in aplastic anemia[J]. Blood, 1998, 91(10): 3582-3592.
16.	Brummendorf TH, Maciejewski JP, Young NS, et al. Telomere length in leukocyte sub-populations of patients with aplastic anemia[J]. Blood, 2001, 97(4): 895-900.
17.	Lee JJ, Kook H, Chung IJ, et al. Telomere length changes in patients with aplastic anaemia[J]. Br J Haematol, 2001, 112(4): 1025-1030.
18.	Du HY, Mason PJ, Bessler M, et al. TINF2 mutations in children with severe aplastic anemia[J]. Pediatr Blood Cancer, 2009, 52(5): 687.
19.	Yamaguchi H, Baerlocher GM, Lansdorp PL, et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemiaand myelodysplastic syndrome[J]. Blood, 2003, 102(3): 916-918.
20.	Fried W, Morley C. Effects of androgenic steroids on erythropoiesis[J]. Steroids, 1985, 46(4-5): 799-826.
21.	Calado RT, Young NS. Telomere disease[J]. N Engl J Med, 2009, 361(24): 2353-2365.
22.	Bacigalupo A, Chaple M, Hows J, et al. Treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party[J]. Br J Haematol, 1993, 83(1): 145-151.
23.	Calado RT, Yewdell WT, Wilkerson KL, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells[J]. Blood, 2009, 114(11): 2236-2243.
24.	Vasa-Nicotera M, Brouilette S, Mangino M, et al. Mapping of a major locus that determines telomere length in humans[J]. Am J Hum Genet, 2005, 76(1): 147-151.
25.	Lee DC, Imm JA, Kim JH, et al. Effect of long-term hormone therapy on telomere length in postmenopausal women[J]. Yonsei Med J, 2005, 46(4): 471-479.

1. 　昝丽娜，李玉云，吴俊英. 再生障碍性贫血发病机制的研究进展[J]. 内科, 2007, 2(5): 828-830.
2. 　申建宾，汤静燕，赵金彩，等. 再生障碍性贫血患者骨髓造血干细胞端粒酶活性异常及其意义的初步研究[J]. 中华血液学杂志, 2001, 22(10): 543-545.
3. 　Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia[J]. Blood, 2006, 108(8): 2509-2519.
4. 　Calado RT, Young NS. Telomere maintenance and human bone marrow failure[J]. Blood, 2008, 111(9): 4446-4455.
5. 　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.
6. 　Frenck RW Jr, Blackburn EH, Shannon KM, et al. The rate of telomere sequence loss in human leukocytes varies with age[J]. Proc Natl Acad Sci USA, 1998, 95(10): 5607–5610．.
7. 　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.
8. 　Aubert G, Lansdorp PM. Telomeres and aging[J]. Physiol Rev, 2008, 88(2): 557-579.
9. 　Bayne S, Liu JP. Hormones and growth factors regulate telomerase activity in ageing and cancer[J]. Mol Cell Endocrinol, 2005, 240(1-2): 11-22.
10. 　Kyo S，Takakura M, Kanaya T, et al. Estrogen activates telomerase[J]. Cancer Res, 1999, 59(23)：5917.
11. 　Misiti S, Nanni S, Fontemaggi G, et al. Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells[J]. Mol Cell Biol, 2000, 20(11): 3764-3771.
12. 　Li H, Zhao L, Yang Z, et al. Telomerase is controlled by protein kinase Calpha in human breast cancer cells[J]. J Biol Chem, 1998, 273(50): 33436-33442.
13. 　Heiss NS, Knight SW, Vulliamy TJ, et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions[J]. Nat Genet, 1998, 19(1): 32-38.
14. 　Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita[J]. Nature, 1999, 402(6761): 551-555.
15. 　Ball SE, Gibson FM, Rizzo S, et al. Progressive telomere shortening in aplastic anemia[J]. Blood, 1998, 91(10): 3582-3592.
16. 　Brummendorf TH, Maciejewski JP, Young NS, et al. Telomere length in leukocyte sub-populations of patients with aplastic anemia[J]. Blood, 2001, 97(4): 895-900.
17. 　Lee JJ, Kook H, Chung IJ, et al. Telomere length changes in patients with aplastic anaemia[J]. Br J Haematol, 2001, 112(4): 1025-1030.
18. 　Du HY, Mason PJ, Bessler M, et al. TINF2 mutations in children with severe aplastic anemia[J]. Pediatr Blood Cancer, 2009, 52(5): 687.
19. 　Yamaguchi H, Baerlocher GM, Lansdorp PL, et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemiaand myelodysplastic syndrome[J]. Blood, 2003, 102(3): 916-918.
20. 　Fried W, Morley C. Effects of androgenic steroids on erythropoiesis[J]. Steroids, 1985, 46(4-5): 799-826.
21. 　Calado RT, Young NS. Telomere disease[J]. N Engl J Med, 2009, 361(24): 2353-2365.
22. 　Bacigalupo A, Chaple M, Hows J, et al. Treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party[J]. Br J Haematol, 1993, 83(1): 145-151.
23. 　Calado RT, Yewdell WT, Wilkerson KL, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells[J]. Blood, 2009, 114(11): 2236-2243.
24. 　Vasa-Nicotera M, Brouilette S, Mangino M, et al. Mapping of a major locus that determines telomere length in humans[J]. Am J Hum Genet, 2005, 76(1): 147-151.
25. 　Lee DC, Imm JA, Kim JH, et al. Effect of long-term hormone therapy on telomere length in postmenopausal women[J]. Yonsei Med J, 2005, 46(4): 471-479.

West China Medical Journal

端粒酶基因突变与再生障碍性贫血

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