SATB1 Defines a Subtype of Cutaneous CD30+ Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile
SATB1 Defines a Subtype of Cutaneous CD30+ Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile
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SATB1 定义了与 T-Helper 17 细胞因子谱相关的皮肤 CD30( ) 淋巴细胞增殖性疾病的亚型
DOI：
10.1016/j.jid.2018.02.028
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发表时间：
2018-08-01
影响因子：
6.5
通讯作者：
Wang, Yang
中科院分区：
文献类型：
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作者：
Sun, Jingru;Yi, Shengguo;Wang, Yang
皮肤CD30(+)淋巴增生性疾病(LPD)，包括淋巴瘤样丘疹(LYP)和原发皮肤间变性大细胞淋巴瘤，是第二常见的皮肤T细胞淋巴瘤。此前，我们报道了胸腺细胞特异性染色质组织者特殊的SATB1在CD30(+)LPD的一部分过度表达并促进恶性T细胞增殖。在这里，我们研究了SATB1在CD30(+)LPD中的表达模式，并探讨了SATB1作为分子标志物对不同临床病理行为的CD30(+)LPD进行分类的可能性。在12例淋巴瘤样丘疹和42例原发皮肤间变性大细胞淋巴瘤中，11例(91.7%)和16例(38.1%)CD30(+)间变性T细胞表达SATB1。SATB1棘突患者表现为T辅助细胞17极化，并伴有更明显的表皮增生和粒细胞浸润。联合应用甲氨蝶呤和干扰素治疗SATB1刺状皮损效果较好。SATB1激活T辅助分子17细胞因子的表达，同时抑制T辅助分子1相关基因的表达。CD30(+)LPD间SATB1表达的异质性与启动子DNA甲基化程度有关。因此，SATB1的表达定义了CD30(+)LPD的一个亚型，具有特征性的病理生物学和预后。这些数据为了解皮肤T细胞恶性肿瘤的异质性提供了有价值的见解，这可能会导致未来的个体化治疗。
Cutaneous CD30(+) lymphoproliferative disorders (LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma, comprise the second most common group of cutaneous T-cell lymphomas. Previously, we reported that special SATB1, a thymocyte-specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30(+) LPDs. Here, we investigated the expression pattern of SATB1 in CD30(+) LPDs with a large cohort of patient samples, and examined the potential of SATB1 as a molecular marker to classify CD30(+) LPDs with differential clinicopathological behaviors. SATB1 expression was identified in the CD30(+) anaplastic T cells in 11 of 12 (91.7%) lymphomatoid papulosis and 16 of 42 (38.1%) primary cutaneous anaplastic large-cell lymphoma cases. SATB1 thorn cases showed T-helper 17 polarization, together with more prominent epidermal hyperplasia and granulocytic infiltration. SATB1 thorn lesions responded better to combined treatment of methotrexate and interferon. SATB1 activated the expression of T-helper 17 cytokines while repressing T-helper 1-related genes. The heterogeneity in SATB1 expression across CD30(+) LPDs was associated with the extent of promoter DNA methylation. Hence, SATB1 expression defines a subtype of CD30(+) LPDs with characteristic pathobiology and prognosis. These data provide valuable insights into the heterogeneity of cutaneous T-cell malignancies, which may lead to individualized therapy in the future.