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

  


Authors: Gao, J.; Zhang, Y.; Yaseen, N. R.; Fang, Y.; Lu, X.; Sukhanova, M.; Chen, Q.; Chen, Y. H.
Article Title: Comprehensive molecular genetic studies of Epstein-Barr virus-negative aggressive Natural killer-cell leukemia/lymphoma
Abstract: 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. © 2020
Keywords: immunohistochemistry; adult; clinical article; human tissue; protein expression; aged; middle aged; human cell; single nucleotide polymorphism; frameshift mutation; missense mutation; clinical feature; disease course; fatigue; nausea; cytogenetics; protein p53; fever; cd2 antigen; cd7 antigen; cd16 antigen; fluorescence in situ hybridization; bone marrow biopsy; microarray analysis; myc protein; splenomegaly; perforin; immunophenotyping; pancytopenia; weakness; lymphocytic infiltration; chromosome analysis; karyotype; cytopenia; lymph node biopsy; lymphadenopathy; nonsense mutation; night sweat; multiple organ failure; fatality; programmed death 1 ligand 1; cd56 antigen; granzyme; ebv; body weight loss; high throughput sequencing; very elderly; human; male; female; article; next-generation sequencing (ngs); tumor necrosis factor receptor superfamily member 8; genetic profile; aggressive nk-cell leukemia/lymphoma; snp microarray; nucleolysin tia 1 isoform p40; aggressive nk cell leukemia; negative staining; severe hepatic impairment
Journal Title: Human Pathology
Volume: 105
ISSN: 0046-8177
Publisher: Elsevier Inc.  
Date Published: 2020-11-01
Start Page: 20
End Page: 30
Language: English
DOI: 10.1016/j.humpath.2020.08.008
PUBMED: 32890601
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091659368&doi=10.1016%2fj.humpath.2020.08.008&partnerID=40&md5=fb8333f9d912aa6c057b5699b202137a
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. Yuqiang Fang
    23 Fang
  2. Yanming Zhang
    199 Zhang
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