Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?
Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?
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DOI：
10.1242/dmm.004010
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发表时间：
2009-09-01
影响因子：
4.3
通讯作者：
Rollins, Barrett J.
中科院分区：
文献类型：
--
作者：
Degar, Barbara A.;Rollins, Barrett J.
朗格汉斯细胞组织细胞增生症（LCH）是一种罕见的增生性疾病，主要发生在儿童时期，涉及表皮的主要抗原呈递细胞的统一名称。LCH可以以多种方式存在，从自发消退的自限性皮疹到死亡率为20%的全身性多器官疾病。由于某些形式的行为在一个相对良性的方式，并与炎症细胞浸润，它已被提出，LCH可能是一种反应性疾病。然而，它的肿瘤性质表明，在LCH的增殖细胞是克隆和过表达p53的事实。尽管如此，没有复发的基因组，遗传或表观遗传异常已被确定。相反，已经描述了与紊乱的朗格汉斯细胞成熟一致的各种分子异常。一个忠实的小动物模型将有助于我们了解LCH的病理生理学，但迄今为止，还不存在。建立模型的挑战包括缺乏典型的复发性遗传异常，以及缺乏真正的组织特异性启动子来驱动遗传元件仅在朗格汉斯细胞中表达。尽管如此，一些粘附分子或趋化因子受体表达的表型异常可能会被建模，具有足够的精度，以允许测试新的治疗方法。
Langerhans cell histiocytosis (LCH) is the unifying designation for a rare proliferative disorder that occurs predominantly in childhood and involves the main antigen-presenting cell of the epidermis. LCH can present in a multitude of ways, from a self-limited rash that resolves spontaneously to a systemic multi-organ disease with a 20% mortality rate. Because some forms behave in a relatively benign manner and are associated with an inflammatory cell infiltrate, it has been proposed that LCH might be a reactive disease. However, its neoplastic nature is suggested by the fact that the proliferating cells in LCH are clonal and overexpress p53. Nonetheless, no recurrent genomic, genetic or epigenetic abnormalities have been identified. Instead, a variety of molecular abnormalities that are consistent with disordered Langerhans cell maturation have been described. A faithful small animal model would aid our understanding of the pathophysiology of LCH but, to date, none exists. Challenges to the creation of a model include the lack of characteristically recurrent genetic abnormalities and the absence of a truly tissue-specific promoter to drive expression of genetic elements solely in Langerhans cells. Still, some of the phenotypic abnormalities in adhesion molecule or chemokine receptor expression might be modeled with sufficient precision to allow the testing of novel therapies.