端粒酶基因突變與再生障礙性貧血_《華西醫學》

作者：

楊程蓉 ,  劉霆

四川大學華西醫院血液內科（成都，610041）;

關鍵詞：

再生障礙性貧血端粒端粒酶端粒酶基因突變雄激素

視頻：

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近年來，端粒酶基因突變引起的端粒酶活性降低和端粒縮短，成為再生障礙性貧血（再障）發病機制的研究熱點之一。大多數獲得性再障患者是由免疫異常引起的，對免疫抑制治療有效。約1/3的再障患者存在端粒縮短、端粒酶活性降低的情況，他們對免疫抑制劑治療通常無效，而對雄激素治療有效。雄激素在人體內可以通過芳香化轉化為雌激素，與端粒酶基因啟動子上的雌激素受體成分相結合而發生作用，從而增加端粒酶活性，恢復骨髓造血和外周血細胞數，彰顯出治療再障的作用。端粒酶基因突變和端粒酶活性異常是現今又一被肯定的再障發病機制，為臨床治療再障開辟了新的思路。

引用本文： 楊程蓉,劉霆. 端粒酶基因突變與再生障礙性貧血. 華西醫學, 2012, 27(7): 1112-1114. doi: 復制

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2.	申建賓，湯靜燕，趙金彩，等. 再生障礙性貧血患者骨髓造血干細胞端粒酶活性異常及其意義的初步研究[J]. 中華血液學雜志, 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.

1. 　昝麗娜，李玉云，吳俊英. 再生障礙性貧血發病機制的研究進展[J]. 內科, 2007, 2(5): 828-830.
2. 　申建賓，湯靜燕，趙金彩，等. 再生障礙性貧血患者骨髓造血干細胞端粒酶活性異常及其意義的初步研究[J]. 中華血液學雜志, 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.

《華西醫學》

端粒酶基因突變與再生障礙性貧血

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《華西醫學》

端粒酶基因突變與再生障礙性貧血

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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