Differences in telomerase expression by the CD1a+ cells in Langerhans cell histiocytosis reflect the diverse clinical presentation of the disease
Differences in telomerase expression by the CD1a+ cells in Langerhans cell histiocytosis reflect the diverse clinical presentation of the disease
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DOI：
10.1002/path.2167
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发表时间：
2007-06-01
影响因子：
7.3
通讯作者：
Annels, N. E.
中科院分区：
文献类型：
--
作者：
da Costa, C. E. T.;Egeler, R. M.;Annels, N. E.
朗格汉斯细胞组织细胞增多症（LCH）是一种以朗格汉斯细胞不受控制的克隆增殖为特征的疾病，其病因尚不清楚。 LCH 的克隆性质可以支持这样的假设：它是一种具有无限生长潜力的肿瘤性疾病。无限增殖的要求之一是维持端粒长度。在一组 70 名患者中，我们着手研究端粒维持机制在 LCH 细胞中是否确实活跃。这项工作表明，通过人端粒逆转录酶 (hTERT) 免疫组织化学评估，来自所有限制性皮肤 LCH 病变 (6/6) 的 LCH 细胞表达端粒酶，而来自分析的大多数骨病变的 LCH 细胞不表达 hTERT (26/34)。有趣的是，与孤立性骨病变相比，来自多系统患者病变的 LCH 细胞始终表达端粒酶 (11/11)，无论病变部位如何。对不同病变部位进行的原位端粒重复扩增方案 (TRAP) 检测表明，该端粒酶具有活性。此外，与hTERT阴性骨单系统LCH病变的LCH细胞相比，hTERT阳性皮肤多系统病变的LCH细胞的端粒长度较长且均匀，后者的长度不均匀。在 hTERT 阴性病变中没有发现端粒延长机制的替代证据。不同病变部位以及孤立性与多系统疾病患者活检中端粒酶表达和端粒长度的差异似乎反映了该疾病不同的临床表现和病程。这项研究的结果对于了解这种疾病的性质具有重要意义。版权所有 (c) 2007 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Langerhans cell histiocytosis (LCH) is a disease characterized by an uncontrolled clonal proliferation of Langerhans cells, whose aetiology is still unclear. The clonal nature of LCH could support the hypothesis that it is a neoplastic disease with unlimited growth potential. One requirement for unlimited proliferation is the maintenance of telomere length. In a group of 70 patients, we set out to investigate whether a telomere maintenance mechanism is indeed active in LCH cells. This work showed that LCH cells from all restricted skin LCH lesions (6/6) expressed telomerase as assessed by human telomere reverse transcriptase (hTERT) immunohistochemistry, whereas LCH cells from the majority of the bone lesions analysed did not express hTERT (26/34). Interestingly, in contrast to the solitary bone lesions, LCH cells from lesions of multi-system patients always expressed telomerase (11/11), regardless of the lesional site. In situ telomeric repeat amplification protocol (TRAP) assays performed on different lesional sites showed that this telomerase was active. In addition, the telomere length of LCH cells from a hTERT-positive skin multi-system lesion was long and homogeneous when compared to that in the LCH cells from hTERT-negative bone single-system LCH lesions, which was heterogeneous in length. No evidence for an alternative lengthening of telomeres mechanism was found in hTERT-negative lesions. The difference in telomerase expression and telomere length at the different lesional sites and in biopsies from patients with solitary versus multi-system disease appears to reflect the diverse clinical presentation and course of this disease. The results from this study have important implications for understanding the nature of this disease. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.