Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma
Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma
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DOI：
10.1016/j.ajpath.2016.02.011
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发表时间：
2016-06-01
影响因子：
6
通讯作者：
Chan, Wing C.
中科院分区：
文献类型：
--
作者：
Kucuk, Can;Hu, Xiaozhou;Chan, Wing C.
自然杀伤/ t细胞淋巴瘤（NKTCL）是一种罕见的侵袭性非霍奇金淋巴瘤，在较晚期的系统性累及时通常无法治愈。克隆诊断标记（例如，独特的T或b细胞受体重排）无法用于NKTCLs。杀伤细胞免疫球蛋白样受体（KIRs）是一类参与抑制或激活NK细胞的I型跨膜糖蛋白。KIRs的限制性表达谱已被提出作为nk细胞增殖的克隆标记物。本研究利用RNA测序技术对NKTCL病例（n = 17）和nk细胞系（n = 3）的所有KIR家族基因和c型凝集素受体基因的转录谱进行了评估。在NKTCL中，除了KIR家族成员杀手igg样受体2DL4 （KIR2DL4，别名CD158D）在大多数（59%）病例中选择性过表达外，所有KIR的表达都倾向于显著降低或缺失。c型凝集素受体未见特异性表达模式。KIR2DL4是KIR家族中不寻常的成员，它识别人类白细胞抗原G，并通过诱导AKT和NF-kappa b等增殖和存活途径介导nk细胞活化。在两种高表达的恶性nk细胞系中，稳定敲低KIR2DL4可显著降低细胞生长。选择性过表达KIR2DL4和下调抑制性KIRs可能参与NKTCL的发病机制。
Natural killer/T-cell lymphoma (NKTCL) is a rare, aggressive form of non-Hodgkin lymphoma that is generally incurable at more advanced stages with systemic involvement. Clonal diagnostic markers (eg, unique T- or B-cell receptor rearrangements) are not available for NKTCLs. Killer cell immunoglobulin Like receptors (KIRs) are a family of type I transmembrane glycoproteins involved in the inhibition or activation of NK cells. A restricted expression profile of KIRs has been proposed as clonal markers of NK-cell proliferations. Here we evaluated the transcription profile of all KIR family genes and C-type lectin receptor genes using RNA sequencing on NKTCL cases (n = 17) and NK-cell lines (n = 3). The expression of all KIRs tended to be markedly reduced or absent in NKTCL, except for the KIR family member killer Ig-like receptor 2DL4 (KIR2DL4; alias CD158D), which was selectively overexpressed in the majority (59%) of cases. No specific expression pattern was observed for C-type Lectin receptors. KIR2DL4 is an unusual member of the KIR family that recognizes human Leukocyte antigen G and mediates NK-cell activation through inducing proliferation and survival pathways such as AKT and NF-kappa B. Stable knockdown of KIR2DL4 in two malignant NK-cell lines with high KIR2DL4 expression significantly reduced cell growth. Selective overexpression of KIR2DL4 and down regulation of inhibitory KIRs may contribute to NKTCL pathogenesis.