自然杂志 ›› 2008, Vol. 30 ›› Issue (3): 128-137.

• 特约专稿 • 上一篇    下一篇

白血病发病原理研究:“多次打击”学说

王月英;陈赛娟   

  1. 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
  • 收稿日期:2008-04-24 修回日期:2008-05-10 出版日期:2008-06-20 发布日期:2008-06-20
  • 通讯作者: 陈赛娟

Study on Leukemogenesis:

WANG Yue-ying; CHEN Sai-juan   

  1. Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Received:2008-04-24 Revised:2008-05-10 Online:2008-06-20 Published:2008-06-20
  • Contact: CHEN Sai-juan

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。

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

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.

Key words:

Multi-hit, chronic myeloid leukemia, acute myeloid leukemia M2b, TEL-AML1-associated childhood acute lymphoblastic leukemia