Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.
Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.
复制标题
DOI：
10.1182/blood.v86.1.38.bloodjournal86138
复制
发表时间：
1995-07
期刊：
影响因子：
20.3
通讯作者：
K. Stegmaier;Shona Pendse;G. Barker;P. Bray-Ward;David C. Ward;Kate T Montgomery;Kenneth S. Krauter;Carol Reynolds;Jeffrey Sklar;Mia Donnelly;Stefan K. Bohlander;Janet D. Rowley;Stephen E. Sallan;D. Gilliland;Todd R. Golub;Bosron Ma
中科院分区：
文献类型：
--
作者：
K. Stegmaier;Shona Pendse;G. Barker;P. Bray-Ward;David C. Ward;Kate T Montgomery;Kenneth S. Krauter;Carol Reynolds;Jeffrey Sklar;Mia Donnelly;Stefan K. Bohlander;Janet D. Rowley;Stephen E. Sallan;D. Gilliland;Todd R. Golub;Bosron Ma
TEL是ETS转录因子家族的新成员，在许多恶性血液病中发生重排，易位涉及染色体12 p13带。在某些情况下，两个TEL等位基因都受到影响，导致白血病细胞中野生型TEL功能的丧失。此外，5%的急性淋巴细胞白血病（ALL）儿童有12 p12-p13缺失，表明肿瘤抑制基因位于12 p上。这些观察结果使我们考虑TEL功能丧失是否可能有助于ALL的发病机制。在这份报告中，我们表明，TEL基因之间的多态性标记D12 S89和D12 S98的地图，我们使用这些侧翼标记筛选配对的诊断和缓解样本81例儿童急性淋巴细胞白血病的杂合性丢失（洛）在TEL基因位点。15%的信息患者显示TEL洛缺失，这在细胞遗传学分析中并不明显。对该位点洛缺失患者的详细检查显示，该严重缺失区域包括两个候选肿瘤抑制基因：TEL和KIP 1，后者是编码细胞周期蛋白依赖性激酶抑制剂p27的基因。这些研究表明TEL位点的洛缺失在儿童ALL中是一个常见的发现。
TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13. In some cases, both TEL alleles are affected, resulting in loss of wild-type TEL function in the leukemic cells. In addition, 5% of children with acute lymphoblastic leukemia (ALL) have 12p12-p13 deletions, suggesting that a tumor suppressor gene resides on 12p. These observations led us to consider whether TEL loss of function may contribute to the pathogenesis of ALL. In this report we show that the TEL gene maps between the polymorphic markers D12S89 and D12S98, and we use these flanking markers to screen paired diagnosis and remission samples from 81 children with ALL for loss of heterozygosity (LOH) at the TEL gene locus. Fifteen percent of informative patients showed TEL LOH which was not evident on cytogenetic analysis. Detailed examination of patients with LOH at this locus showed that the critically deleted region included two candidate tumor suppressor genes: TEL and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. These studies show that LOH at the TEL locus is a frequent finding in childhood ALL.