UNIQUE FUSION OF BCR AND C-ABL GENES IN PHILADELPHIA-CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA
UNIQUE FUSION OF BCR AND C-ABL GENES IN PHILADELPHIA-CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA
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DOI：
10.1016/0092-8674(87)90007-9
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发表时间：
1987-10-09
期刊：
影响因子：
64.5
通讯作者：
GROSVELD, G
中科院分区：
文献类型：
--
作者：
HERMANS, A;HEISTERKAMP, N;GROSVELD, G
费城（Ph）染色体，t（9：22）的产物，是慢性粒细胞白血病的细胞遗传学标志。9号染色体上的c-abl癌基因易位到Ph染色体上，并与断裂点簇区（bcr）相连，该断裂点簇区是大bcr基因的一部分。这导致bcr-c-abl融合基因的形成，其被转录成编码210 kd bcr-c-abl融合蛋白的8.5 kb嵌合mRNA。Ph染色体也见于急性淋巴细胞白血病（Ph+ ALL）。虽然c-abl易位，并已确定了一个新的190 kd c-abl蛋白，没有断点中观察到bcr（Ph+bcr- ALL）。我们发现在Ph+bcr- ALL中，22号染色体上的断裂点位于同一bcr基因内，但更多位于bcr的5“”处。嵌合bcr-c-abl cDNA的克隆表明，融合基因被转录成一个7 kb的mRNA，编码一种新的融合蛋白。
The Philadelphia (Ph) chromosome, the product of t(9:22), is the cytogenetic hallmark of chronic myelogenous leukemia. The c-abl oncogene on chromosome 9 is translocated to the Ph chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The Ph chromosome is also found in acute lymphoblastic leukemic (Ph+ ALL). Although the c-abl is translocated and a new 190 kd c-abl protein has been identified, no breakpoints are observed in the bcr (Ph+bcr- ALL). Here we show that in Ph+bcr- ALL, breakpoints in chromosome 22 occur within the same bcr gene, but more 5'' of the bcr. Cloning of a chimeric bcr-c-abl cDNA demonstrates that the fusion gene is transcribed into a 7 kb mRNA, encoding a novel fusion protein.