摘要
近50%的急性髓系白血病可以找到染色体易位,常见的染色体易位是t(8;21)(q22;q22)。这种易位使21号染色体上的aml1(runx1)基因与8号染色体上的eto(mtg8,runx1t1)基因相互融合形成aml1/eto融合基因。最初对于t(8;21)急性髓系白血病发病机制的研究一直着重在造血转录激活因子AML1转化为白血病抑制因子,在靶基因调控水平上阻碍髓系细胞分化,aml1/eto融合基因在造血分化过程关键点抑制作为肿瘤抑制因子的造血转录因子。目前认为,t(8;21)染色体易位及二次突变引起造血干细胞减少的系别限制性及基因组不稳定性是引发aml1/eto融合基因阳性白血病的主要原因。本文就aml1/eto融合基因及其剪接变异体在调控干细胞更新、阻断造血分化及与各造血系统特异的转录因子相互作用的分子机制进行综述。
Acquired chromosomal translocations can be identified in nearly 50% of human acute myeloid leukemias. The common chromosomal translocation in this disease is t（8;21）（q22;q22）. It involves the aml1 （runx1） gene on chromosome 21 and the eto （mtg8, runx1t1） gene on chromosome 8 generating the aml1/eto fusion gene. An initial model for its pathogenesis emphasized the conversion of a hematopoietic transcriptional activator AML1 into a leukemogenic repressor which blocked myeloid differentiation at the level of target gene regulation. Aml1/eto fusion genes inhibit key hematopoietic transcription factor that function as tumor suppressors at several nodal point during hematopoietic differentiation. A new model is presented in which aml1/eto coordinates expansion of the stem cell compartment with diminished lineage commitment and with genome instability. In this review, the molecular role of aml1/eto fusion gene and his transcribed isoforms in regulating stem renewal, blocking hematopoietic differentiation and interacting with various lineage-specific transcription factors are summarized.
出处
《中国实验血液学杂志》
CAS
CSCD
2010年第6期1632-1637,共6页
Journal of Experimental Hematology
