GENERATION OF THE AML1-EVI-1 FUSION GENE IN THE T(3 21)(Q26 Q22) CAUSES BLASTIC CRISIS IN CHRONIC MYELOCYTIC-LEUKEMIA
GENERATION OF THE AML1-EVI-1 FUSION GENE IN THE T(3 21)(Q26 Q22) CAUSES BLASTIC CRISIS IN CHRONIC MYELOCYTIC-LEUKEMIA
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DOI：
10.1002/j.1460-2075.1994.tb06288.x
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发表时间：
1994-02-01
期刊：
影响因子：
11.4
通讯作者：
HIRAI, H
中科院分区：
文献类型：
--
作者：
MITANI, K;OGAWA, S;HIRAI, H
t（3; 21）（q26; q22）易位是慢性粒细胞白血病（CML）急变中发现的一致性染色体异常之一，被认为在CML向急性急变期的白血病进展中发挥重要作用。AML 1基因位于急性髓细胞白血病中发现的t（8;21）（q22;q22）易位的易位断裂点，也被t（3;21）（q26;q22）易位重排。对携带t（3;21）的白血病细胞系细胞（SKH 1）的cDNA文库进行筛选，分离出两个潜在完整的AML 1-EVI-1嵌合cDNA（6 kb）。在SKH 1细胞中检测到8.2和7.0kb的两种AML 1-EVI-1融合转录物。这些细胞表达180 kDa的AML 1-EVI-1融合蛋白，该融合蛋白含有AML 1的N-末端一半，包括与整个锌指EVI-1蛋白融合的runt同源结构域。通过基于RNA的PCR检测，AML 1-EVI-1融合转录本在所有三例携带t（3;21）的白血病中是一致的。这些发现有力地表明t（3;21）易位导致一类新的嵌合转录因子的形成，其可能通过干扰细胞生长和分化而促进CML的白血病进展。
The t(3;21)(q26;q22) translocation, which is one of the consistent chromosomal abnormalities found in blastic crisis of chronic myelocytic leukemia (CML), is thought to play an important role in the leukemic progression of CML to an acute blastic crisis phase. The AML1 gene, which is located at the translocation breakpoint of the t(8;21)(q22;q22) translocation found in acute myelocytic leukemia, was also rearranged by the t(3;21)(q26;q22) translocation. Screening of a cDNA library of the t(3;21)-carrying leukemic cell line cells (SKH1) resulted in the isolation of two potentially complete AML1-EVI-1 chimeric cDNAs of 6 kb. Two species of AML1-EVI-1 fusion transcripts of 8.2 and 7.0 kb were detected in SKH1 cells. These cells expressed the 180 kDa AML1-EVI-1 fusion protein containing an N-terminal half of AML1 including a runt homology domain which is fused to the entire zinc finger EVI-1 protein. The AML1-EVI-1 fusion transcript was consistent in all three cases of the t(3;21)-carrying leukemia examined by RNA-based PCR. These findings strongly suggest that the t(3;21) translocation results in the formation of a new class of chimeric transcription factor which could contribute to the leukemic progression of CML through interference with cell growth and differentiation.