Cell(s) of Origin of Langerhans Cell Histiocytosis.
Cell(s) of Origin of Langerhans Cell Histiocytosis.
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DOI：
10.1016/j.hoc.2015.06.003
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Allen CE
中科院分区：
文献类型：
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作者：
Collin M;Bigley V;McClain KL;Allen CE
朗格汉斯细胞组织细胞增生症（LCH）是一种诊断，包括广泛的临床表现，其特征是常见的炎性病变，含有克隆性CD 1a+朗格林+（CD 207）组织细胞或LCH细胞。基于LCH细胞和表皮朗格汉斯细胞（LC）的表型相似性，发病机制的模型集中在表皮LC分化的畸变上。最近，在大多数LCH和ERK磷酸化的情况下，已经发现激活体细胞突变的MAPK途径似乎是普遍的LCH细胞。使用BRAF V600E突变作为谱系标记，新出现的数据支持这样一种模型，即在自我更新的造血祖细胞中MAPK激活可能驱动播散性高风险疾病，而在更分化的定型髓样前体细胞或外周组织髓样细胞群中MAPK激活可能诱导多灶性或单灶性低风险LCH。因此，具有共同组织学的异质性临床表现可能代表了获得性分化缺陷的最终共同途径，起始于多个点。该模型的意义包括将LCH重新定义为髓样肿瘤，并将治疗策略重新聚焦于细胞和起源谱系。
Langerhans cell histiocytosis (LCH) is a diagnosis encompassing a wide spectrum of clinical manifestations, characterized by the common finding of inflammatory lesions containing clonal CD1a+ Langerin+ (CD207) histiocytes or LCH cells. Based on phenotypic similarity of LCH cells and epidermal Langerhans cells (LCs), models of pathogenesis have focused on aberrations in the differentiation of epidermal LCs. Recently, activating somatic mutations in the MAPK pathway have been discovered in the majority of cases of LCH and ERK phosphorylation appears to be universal in LCH cells. Using the BRAF V600E mutation as a lineage marker, emerging data support a model in which MAPK activation in self-renewing hematopoietic progenitors may drive disseminated high-risk disease, whereas MAPK activation in more differentiated committed myeloid precursors or peripheral tissue myeloid populations may induce multifocal or unifocal low-risk LCH. The heterogeneous clinical manifestations with shared histology may therefore represent the final common pathway of an acquired defect of differentiation, initiated at more than one point. Implications of this model include re-definition of LCH as a myeloid neoplasia and re-focusing therapeutic strategies on the cells and lineages of origin.