皮肤T细胞淋巴瘤(CTCL)是由恶性T细胞渗入皮肤引起的一系列淋巴增殖性疾病。CTCL最常见的变体包括真菌病(MF),Sézary综合征(SS)和CD30+淋巴增生性疾病(CD30+LPDs)。CD30+LPD包括原发性皮肤间变性大细胞淋巴瘤(pcALCL),淋巴瘤样丘疹病(LyP)和临界CD30+LPD。MF的频率,SS和CD30+LPDs约为40-50%,<5%和~10-25%,分别。尽管最近取得了进展,CTCL的诊断仍然具有挑战性。CTCL癌变的机制仍有待充分阐明。因此,在患者来源的细胞系和异种移植/基因工程小鼠模型(GEMM)中进行的实验对于促进我们对疾病发病机理的理解至关重要.为了实现这一点,了解每个单独的模型系统的复杂性和局限性是非常重要的。目前,11个永生化的患者来源的细胞系和不同的异种移植物/GEMM正在用于研究CTCL的发病机理,并在临床试验之前评估各种治疗方式的疗效。基因表达研究,细胞系的核型分析证明了SeAx的分子特征,Sez4,SZ4,H9和Hut78与SS起源一致;MyLa和HH类似于高级MF的分子谱,而Mac2A和PB2B代表CD30+LPDs。其他两种常用的人类T细胞嗜淋巴细胞病毒-1(HTLV-1)细胞系的分子分析,发现MJ和Hut102具有成人T细胞白血病/淋巴瘤(ATLL)的特征。在小鼠模型中的研究表明,使用MyLa可以生长异种移植肿瘤,HH,NSG(NODScidgamma小鼠)小鼠的H9、Hut78、PB2B和SZ4细胞,虽然建立了几个额外的实验性GEMM来研究发病机理,药物和炎性细胞因子在CTCL中的作用。本综述总结了用于研究和理解CTCL的病因和异质性的细胞系和异种移植/GEMM。
Cutaneous T cell lymphoma (CTCL) is a spectrum of lymphoproliferative disorders caused by the infiltration of malignant T cells into the skin. The most common variants of CTCL include mycosis fungoides (MF), Sézary syndrome (SS) and CD30+ Lymphoproliferative disorders (CD30+ LPDs). CD30+ LPDs include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP) and borderline CD30+ LPD. The frequency of MF, SS and CD30+ LPDs is ~40-50%, <5% and ~10-25%, respectively. Despite recent advances, CTCL remains challenging to diagnose. The mechanism of CTCL carcinogenesis still remains to be fully elucidated. Hence, experiments in patient-derived cell lines and xenografts/genetically engineered mouse models (GEMMs) are critical to advance our understanding of disease pathogenesis. To enable this, understanding the intricacies and limitations of each individual model system is highly important. Presently, 11 immortalized patient-derived cell lines and different xenograft/GEMMs are being used to
study the pathogenesis of CTCL and evaluate the therapeutic efficacy of various treatment modalities prior to clinical trials. Gene expression studies, and the karyotyping analyses of cell lines demonstrated that the molecular profile of SeAx, Sez4, SZ4, H9 and Hut78 is consistent with SS origin; MyLa and HH resemble the molecular profile of advanced MF, while Mac2A and PB2B represent CD30+ LPDs. Molecular analysis of the other two frequently used Human T-Cell Lymphotropic Virus-1 (HTLV-1)+ cell lines, MJ and Hut102, were found to have characteristics of Adult T-cell Leukemia/Lymphoma (ATLL). Studies in mouse models demonstrated that xenograft tumors could be grown using MyLa, HH, H9, Hut78, PB2B and SZ4 cells in NSG (NOD Scid gamma mouse) mice, while several additional experimental GEMMs were established to
study the pathogenesis, effect of drugs and inflammatory cytokines in CTCL. The current review summarizes cell lines and xenograft/GEMMs used to
study and understand the etiology and heterogeneity of CTCL.