Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26).
Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26).
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DOI：
10.1182/blood.v84.8.2681.bloodjournal8482681
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发表时间：
1994-10
期刊：
影响因子：
20.3
通讯作者：
K. Suzukawa;E. Parganas;A. Gajjar;Tsukasa Abe;S. Takahashi;Kenzaburo Tani;Shigetaka Asano;H. Asou;Nanao Kamada;Jun Yokota
中科院分区：
文献类型：
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作者：
K. Suzukawa;E. Parganas;A. Gajjar;Tsukasa Abe;S. Takahashi;Kenzaburo Tani;Shigetaka Asano;H. Asou;Nanao Kamada;Jun Yokota
约2%的急性髓细胞性白血病（AML）或骨髓增生异常综合征（MDS）患者的3号染色体长臂发生结构改变。主要的改变是inv（3）（q21 q26）和t（3：3）（q21;q26），通常被归类为3q 21 q26综合征。我们以前曾报道过，在t（3;3）（q21;q26）和inv（3）（q21 q26）的AML中，EVI 1基因被转录激活，并且在易位的3q 26处的染色体断裂点是EVI 1基因的5'，而在倒位病例中的断裂点是基因的3'。在这些研究中，另外4例伴有inv（3）（q21 q26）的AML病例显示表达EVI 1基因，并在该基因的3'端具有断点。为了表征3q 21断裂点区域，分离覆盖约100 kb的粘粒和噬菌体克隆。在3q 21处，发现具有t（3;3）（q21;q26）和inv（3）（q21 q26）的AML的断裂点聚集在Ribophorin I基因下游约50 kb的区域上。结果表明一个共同的易位和倒位机制，并支持这一假设，即EVI 1基因的转录激活介导的增强子元件与核糖体蛋白I基因。
Structural alterations occur in the long arm of chromosome 3 in approximately 2% of patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). The major alterations are inv(3)(q21q26) and t(3:3)(q21;q26) and are often classified as the 3q21q26 syndrome. We previously reported that the EVI1 gene is transcriptionally activated in AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) and that the chromosomal breakpoints at 3q26 in the translocations were 5' of the EVI1 gene, whereas the breakpoints in the inversion cases were 3' of the gene. In these studies, four additional cases of AML with inv(3)(q21q26) are shown to express the EVI1 gene and to have breakpoints 3' of the gene. To characterize the 3q21 breakpoint region, cosmid and phage clones were isolated that cover approximately 100 kb. At 3q21, the breakpoints for both AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) were found to cluster over a region of approximately 50 kb downstream of the Ribophorin I gene. The results indicate a common mechanism for the translocations and inversions and support the hypothesis that the transcriptional activation of the EVI1 gene is mediated by enhancer elements associated with the Ribophorin I gene.