Stegmaier K, Pendse S, Barker G F, Bray-Ward P, Ward D C, Montgomery K T, Krauter K S, Reynolds C, Sklar J, Donnelly M
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Blood. 1995 Jul 1;86(1):38-44.
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.
TEL是ETS转录因子家族的新成员，在许多血液系统恶性肿瘤中发生重排，伴有涉及染色体带12p13的易位。在某些情况下，两个TEL等位基因均受影响，导致白血病细胞中野生型TEL功能丧失。此外，5%的急性淋巴细胞白血病（ALL）儿童有12p12 - p13缺失，提示12p上存在一个肿瘤抑制基因。这些观察结果促使我们思考TEL功能丧失是否可能参与ALL的发病机制。在本报告中，我们表明TEL基因定位于多态性标记D12S89和D12S98之间，并且我们使用这些侧翼标记筛选81例ALL儿童的配对诊断和缓解样本，以检测TEL基因座处的杂合性缺失（LOH）。15%的信息充分的患者显示出TEL LOH，这在细胞遗传学分析中并不明显。对该基因座处有LOH的患者进行详细检查发现，关键缺失区域包括两个候选肿瘤抑制基因：TEL和KIP1，即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基因座处的LOH在儿童ALL中很常见。
