| 白血病发病原理研究：“多次打击”学说 |
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| 引用本文： | 王月英,陈赛娟. 白血病发病原理研究：“多次打击”学说[J]. 自然杂志, 2008, 30(3): 128-137 |
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| 作者姓名： | 王月英 陈赛娟 |
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| 作者单位： | 上海交通大学医学院附属瑞金医院，上海血液学研究所，上海200025 |
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| 摘 要： | 白血病是一种基因组发生动态变化的造血干/祖细胞疾病，染色体易位和/或基因突变是常见的遗传学异常。近来，研究提示白血病的发生多遵循“多次打击”模式。在慢性粒细胞白血病中，GATA-2突变可能与BCR-ABL共同作用导致“急变”；在M2b型急性髓性白血病中，C-KIT突变可能是在AML-ETO基础上的再次遗传学异常；在TEL-AML1相关的儿童急性淋病细胞白血病中，正常TEL基因丢失作为第二次打击而致病。作者以上述三种白血病为例，阐述其发病原理以及靶向治疗研究所取得的进展。
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| 关 键 词： | 多次打击 慢性粒细胞白血病 M2b型急性髓性白血病 TEL-AML1相关的儿童急性淋病细胞白血病 |
| 收稿时间： | 2008-04-24 |
| 修稿时间： | 2008-05-10 |
Study on Leukemogenesis: "Multi-Hit" Hypothesis |
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| WANG Yue-ying,CHEN Sai-juan. Study on Leukemogenesis: "Multi-Hit" Hypothesis[J]. Chinese Journal of Nature, 2008, 30(3): 128-137 |
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| Authors: | WANG Yue-ying CHEN Sai-juan |
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| Affiliation: | Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China |
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| Abstract: | Leukemia represents a group of diseases of hematopoietic stem/progenitor cells with dynamic changed such as chromosomal translocations and/or gene mutations. Recently,evidences suggest that acute myeloid leukemia follow a "Multi-hit"model in leukemogenesis. Acquisition of GATA-2 mutations other than BCR/ABL fusion gene may cause disease progression from chronic myeloid leukemia to acute transformation. AML1-ETO represents the first, fundamental genetic hit to initiate the disease,wheresa C-KIT mutation may be a second hit for the development of acute myeloid leukemia M2 with t(8;21).TEL-AML1 functions as a first genetic event,the additional loss of the normal TEL allele may cause full-brown leukemia which mainly occurs in childhood acute lymphoblastic leukemia. The new progress of leukemias in pathpgenesis and targeted therapy are summarized. |
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| Keywords: | Multi-hit chronic myeloid leukemia acute myeloid leukemia M2b TEL-AML1-associated childhood acute lymphoblastic leukemia |
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