Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Hum Pathol. 2020 Nov;105:20-30. doi: 10.1016/j.humpath.2020.08.008. Epub 2020 Sep 2.
EBV-negative aggressive NK-cell leukemia/lymphoma (ANKL) is a recently recognized, rare NK-cell neoplasm that preferentially affects non-Asians and has a fulminant clinical course. Little is known about the genetic alterations of this disease. In this study, we performed comprehensive molecular genetic studies, including chromosomal analysis, fluorescence in situ hybridization, single nucleotide polymorphism (SNP) microarray, and next-generation sequencing (NGS), on 4 patients diagnosed in our institution. The results demonstrated that our EBV-negative ANKLs have highly complex genomic profiles characterized by near-triploid/near-tetraploid karyotype (3 of 3) with numerous structural abnormalities, inactivation of TP53 (3 of 3), overexpression of c-Myc (4 of 4), strong expression of PD-L1 in neoplastic cells (2 of 4), and gain of the 11q23-ter region (2 of 2). Our study provides important insights of EBV-negative ANKL, which share many of the genetic features with their EBV-positive counterpart. The strong expression of Programmed death-ligand 1 (PD-L1) suggests that immune checkpoint inhibitors may be further explored as a potential therapeutic option for this highly aggressive, chemotherapy-resistant NK-cell neoplasm.
EBV 阴性侵袭性 NK 细胞白血病/淋巴瘤（ANKL）是一种新近被认识的、罕见的 NK 细胞肿瘤，主要影响非亚洲人群，且具有暴发性的临床病程。目前对于这种疾病的遗传学改变知之甚少。在这项研究中，我们对 4 名在我院确诊的患者进行了全面的分子遗传学研究，包括染色体分析、荧光原位杂交、单核苷酸多态性（SNP）微阵列和下一代测序（NGS）。结果表明，我们的 EBV 阴性 ANKL 具有高度复杂的基因组特征，表现为近三倍体/近四倍体核型（3/3），存在大量结构异常，TP53 失活（3/3），c-Myc 过表达（4/4），肿瘤细胞中 PD-L1 强表达（2/4），11q23-ter 区域获得（2/2）。我们的研究为 EBV 阴性 ANKL 提供了重要的见解，其与 EBV 阳性 ANKL 具有许多相似的遗传特征。程序性死亡配体 1（PD-L1）的强表达提示免疫检查点抑制剂可能作为一种潜在的治疗选择，用于治疗这种高度侵袭性、对化疗耐药的 NK 细胞肿瘤。
