AML1 gene amplification: a novel finding in childhood acute lymphoblastic leukemia.
AML1 gene amplification: a novel finding in childhood acute lymphoblastic leukemia.
复制标题
AML1 基因扩增：儿童急性淋巴细胞白血病的新发现。
作者：
T. Niini;J. Kanerva;K. Vettenranta;U. Saarinen;S. Knuutila
背景和目标
我们之前通过比较基因组杂交发现两名患有急性淋巴细胞白血病 (ALL) 的儿童的染色体区域 21q22 存在高水平扩增。同一区域含有 AML1 基因。本研究的目的是调查 AML1 是否是这些扩增中的靶基因。
设计与方法
骨髓样本取自 112 名儿童 ALL 患者。使用荧光原位杂交与特异于 AML1 和 TEL 基因的双色 DNA 探针研究 AML1 的拷贝数。
结果
通过比较基因组杂交，其中 3 名患者的 AML1 扩增了 3 至 8 倍，并显示 21q22 高水平扩增。其中两个患者的额外拷贝串联位于 21 号染色体的衍生物中。37 名患者 (33%) 有 1 到 2 个额外的 AML1 拷贝，很可能反映了 21 三体性和 21 四体性的发生率。与没有额外拷贝的患者相比，具有额外 AML1 拷贝的患者 (7/40; 18%) 的 TEL-AML1 融合频率较低(24/72；33%)。 AML1 扩增 3 至 8 倍的三名患者均未表现出 TEL 融合或丢失。
解释和结论
我们的研究结果表明，AML1 基因是儿童 ALL 21q22 扩增子中的靶基因。为了了解 AML1 扩增在白血病发生中的作用（如果有的话），需要进一步研究。
BACKGROUND AND OBJECTIVE
We previously found a high-level amplification in chromosomal region 21q22 in two children with acute lymphoblastic leukemia (ALL) using comparative genomic hybridization. The same region harbors the AML1 gene. The aim of the present study was to investigate whether AML1 is a target gene in these amplifications.
DESIGN AND METHODS
Bone marrow samples were obtained from 112 childhood ALL patients. The copy number of AML1 was studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes.
RESULTS
Three of the patients had 3-to-8 fold amplification of AML1 and showed a high-level amplification of 21q22 by comparative genomic hybridization. In two of them the extra copies were shown to be located tandemly in a derivative of chromosome 21. Thirty-seven of the patients (33%) had 1-to-2 extra copies of AML1, most probably reflecting the incidence of trisomy 21 and tetrasomy 21. The TEL-AML1 fusion was less frequent in the patients with extra copies of AML1 (7/40; 18%) than in the patients with no extra copy (24/72; 33%). None of the three patients with 3-to-8 fold amplification of AML1 showed the fusion or loss of TEL.
INTERPRETATION AND CONCLUSIONS
Our findings suggest that the AML1 gene is a target gene in the 21q22 amplicon in childhood ALL. To understand the role, if any, of the AML1 amplification in leukemogenesis, further studies are needed.
DOI：
10.1073/pnas.92.11.4917
发表时间：
1995-05-23
影响因子：
11.1
作者：
GOLUB, TR;BARKER, GF;GILLILAND, DG
通讯作者：
GILLILAND, DG