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Study on the etiological role of 11q23 region abnormalities of infant leukemic cells

婴儿白血病细胞11q23区域异常的病因学作用研究

基本信息

批准号：
11670764
负责人：
UEDA Kazuhiro
金额：
$ 2.24万
依托单位：
HIROSHIMA UNIVERSITY
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-11670764/
关键词：
Infant leukemia 11q23 anormaly rearrangement of MLL gene FISH analysis MLL遺伝子

项目摘要

The purpse of this study is to detect a new oncogene in 11q23 region, which has leukemogenic effect in infant leukemia, using a FISH analysis. In infant leukemia study of Japan, 61 cases of infant acute lymphoblastic leukemia were enrolled. Thirty four cases showed chromosomal abnormality in 11q23 region. A t(4 ; 11) was found in 23 cases, t(11 ; 19) in 4, t(9 ; 11) in 3, other abnormality in 4, respectively. MLL gene rearrangement were detected in 68% of ALL cases with southern blott analysis, especially 83% of cases under 6 months old. Except a case with inv(11)(p13q23), all cases with 11q23 abnormality had MLL gene rearrangement. In AML cases, 11q23 abnormality were detected in 11 of 21 cases with FAB M4/5, and all 11 cases had reciprocal translocation. MLL gene rearrangement were detected in 12 cases including 11 cases with 11q23 abnormality. One of 10 cases without FAB M4/5 had MLL gene rearrangement. And only a ALL case with inv(11)(p13q23) showed 11q23 abnormality without MLL gene rearrangement. Howeber, FISH analysis with CD3YAC prove revealed MLL gene rearrangement in this case. Additional southern blott analysis with Eco RI digestion confirmed MLL gene rearrangement in the case. Then, 11q23 abnormality is correlated with MLL rearrangement in infant leukemia. Next, we studied ALL with normal karyotype and MLL gene rearragement in three cases by dual color FISH analysis. Using the method, masked t(4 ; 11) was detected in 2 cases, and masked t(10 ; 11) in one. These data suggested that molecular analysis must be done in infant leukemia even with normal karyotype, and dual color FISH analysis is useful for detecting masked chromosomal translocations.

本研究的目的是利用荧光原位杂交技术检测11 q23区一个新的癌基因，该基因在婴儿白血病中具有致白血病作用。在日本的婴儿白血病研究中，纳入了61例婴儿急性淋巴细胞白血病。34例11 q23区染色体异常。t（4 ; 11）23例，t（11 ; 19）4例，t（9 ; 11）3例，其他异常4例。Southern杂交结果显示，68%的ALL患儿存在MLL基因重排，尤其是6个月以下患儿的MLL基因重排率高达83%。除1例inv（11）（p13 q23）外，所有11 q23异常者均存在MLL基因重排。AML中FAB M4/5型11例11 q23异常，均为相互易位。MLL基因重排12例，其中11例伴有11 q23异常。10例FAB M4/5阴性者中1例MLL基因重排。1例伴inv（11）（p13 q23）的ALL患者11 q23异常，无MLL基因重排。而CD 3 YAC的FISH检测证实了MLL基因重排。用EcoRI消化的附加Southern印迹分析证实了该病例中的MLL基因重排。11 q23异常与婴儿白血病MLL重排相关。其次，我们对三例核型正常、MLL基因重排的ALL进行了双色FISH分析。应用该方法，在2例病例中检测到掩蔽t（4 ; 11），在1例病例中检测到掩蔽t（10 ; 11）。这些数据表明，即使核型正常的婴儿白血病也必须进行分子分析，双色FISH分析对检测掩蔽的染色体易位是有用的。