The importance of Notch signaling in peripheral T-cell lymphomas
The importance of Notch signaling in peripheral T-cell lymphomas
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DOI：
10.3109/10428194.2013.807510
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发表时间：
2014-03-01
影响因子：
2.6
通讯作者：
Gniadecki, Robert
中科院分区：
文献类型：
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作者：
Kamstrup, Maria Rorbaek;Biskup, Edyta;Gniadecki, Robert
外周T细胞淋巴瘤（PTL）代表了高医疗需求的领域。以前，我们证明了Notch（一种已知的癌基因）在原发性皮肤间变性大细胞淋巴瘤（ALCL）中的高表达。在这项研究中，我们对PTL-NOS和系统性ALCL的淋巴结进行了Notch 1的免疫组织化学染色，（ALK+和ALK-），并报告了三个亚组之间的相似分布：PTL-NOS阴性、中度和强阳性表达率分别为18%、27%和55 ALCL ALK阳性10例，阳性率分别为20%、0%和80%; ALCL ALK-9例，阳性率分别为45%、22%和33%（p > 0.05）。在ALK+ ALCL细胞系Karpas-299中，在细胞活力和细胞凋亡方面，使用γ-分泌酶抑制剂（GSI）I对Notch的药理学抑制作用远强于GSI IX、XX和XXI。总之，PTL肿瘤细胞具有显着的Notch 1表达，并且Notch抑制剂治疗具有细胞毒性作用。
Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL not otherwise specified (PTL-NOS) and systemic ALCL (ALK+ and ALK-) and report a similar distribution among the three subgroups: Negative, moderate and strong expression was, respectively, 18%, 27% and 55% for PTL-NOS (33 cases), 20%, 0% and 80% for ALCL ALK+ (10 cases) and 45%, 22% and 33% for ALCL ALK- (nine cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with gamma-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment with Notch inhibitors has cytotoxic effects.