Comprehensive molecular genetic studies of Epstein-Barr virus-negative aggressive Natural killer-cell leukemia/lymphoma

Juehua Gao*, Yanming Zhang, Nabeel R. Yaseen, Yuqiang Fang, Xinyan Lu, Madina Sukhanova, Qing Chen, Yi Hua Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)20-30
Number of pages11
JournalHuman pathology
StatePublished - Nov 2020


  • Aggressive NK-cell leukemia/lymphoma
  • Cytogenetics
  • EBV
  • Next-generation sequencing (NGS)
  • SNP microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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