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Searching for gene responsible for adult T-cell leukemia(ATL)from human chromosome 14 at q32 region.

从人类14号染色体q32区域寻找导致成人T细胞白血病（ATL）的基因。

基本信息

批准号：
11672251
负责人：
ISOBE Masaharu
金额：
$ 2.3万
依托单位：
Toyama University, Faculty of Engineering
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672251/
关键词：
adult T-cell leukemia chromosome 14 chromosome abnormalities ATLl 成人T細胞白血病 ATL

项目摘要

Adult T cell leukemia/lymphoma(ATLL)are frequently found in southwest part of Japan, in which it has been thought to be caused by HTLV-I virus due to the close association between viral infection and ATLL.However, the fact of no gene expression on HTLV-I virus detected in leukemic cells indicates that the change of the cellular gene expression is indispensable for the genesis of ATLL.From the cytogenetic analysis, it has been reported that about 15% of ATLL cases have abnormalities of chromosome 14 at band q32 region. However, the molecular details these abnormalities were completely unknown. Thus, we have investigated 14q32 abnormalities in 50 cases of ATLL using fluorescence in situ hybridization (FISH)method to clarify the molecular details of these abnormalities and to find the region of favorite site for chromosomal aberration where genes responsible for the genesis of ATLL may be reside. As the results, we have found following points. 1)Either 2 or 3copies of amplification of 14q32 region can be found in about 60% of acute and lymphoma type of ATLL but not found in chronic type. 2)The chromosome abnormalities involved in immunogloblin heavy chain locus can be found in about 4% of ATLL cases. 3)In about 22% of ATLL cases, the chromosome rearrangement occurred in the region between TCLl and D14S16 loci. 4)There are at least three clusters of breakpoints derived from these chromosome rearrangements within this region. By conducting further investigation on one of these clusters, we have found a new gene, which we named as ATLl, is a candidate of ATLL related gene. Because the rearrangments of ATLl gene can be found in 8% of ATLL cases.

成人T细胞白血病/淋巴瘤(ATLL)是日本西南部常见的T细胞白血病/淋巴瘤，因其与病毒感染密切相关而被认为是由HTLV-I病毒引起的。然而，在白血病细胞中检测到HTLV-I病毒无基因表达的事实表明，细胞基因表达的改变是ATLL发生所不可缺少的。从细胞遗传学分析来看，约15%的ATLL病例存在14号染色体q32区异常。然而，这些异常的分子细节是完全未知的。因此，我们用荧光原位杂交(FISH)方法对50例ATLL的14q32异常进行了研究，以阐明这些异常的分子细节，并寻找与ATLL的发生有关的基因可能存在的染色体异常的最好部位。作为结果，我们发现了以下几点。1)约60%的急性和淋巴瘤型ATLL可见2个或3个拷贝的14q32区扩增，而在慢性型中未见。2)免疫球蛋白重链基因涉及的染色体异常约占4%。3)TCL1和D14S16基因座之间的染色体重排发生率约为22%。4)在这个区域内，至少有三个断裂点是由这些染色体重排产生的。通过对其中一个簇的进一步研究，我们发现了一个新的基因，我们命名为atll，它是atll相关基因的候选基因。因为AT11基因重排出现在8%的ATLL病例中。