The Genomics and Molecular Biology of Natural Killer/T-Cell Lymphoma: Opportunities for Translation

International Journal of Molecular Sciences

Tae-Hoon Chung¹  AnandD. Jeyasekharan²  Wee-Joo Chng²  Sanjay de Mel²  GwynethShook-Ting Soon³  Yingting Mok³  Siok-Bian Ng³ 

[1] Cancer Science Institute of Singapore, National University of Singapore, Singapore 110974, Singapore;Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore 110974, Singapore;Department of Pathology, National University Hospital, National University Health System, Singapore 110974, Singapore;

关键词: NK/T-cell lymphoma;    genomics;    Gene expression profiling (GEP);    copy number;    epigenetics;    immune checkpoint;    targeted therapy;   

DOI  :  10.3390/ijms19071931

来源: DOAJ

【 摘 要 】

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is an aggressive malignancy with a poor prognosis. While the introduction of L-asparaginase in the treatment of this disease has significantly improved the prognosis, the outcome of patients relapsing after asparaginase-based chemotherapy, which occurs in up to 50% of patients with disseminated disease, remains dismal. There is hence an urgent need for effective targeted therapy especially in the relapsed/refractory setting. Gene expression profiling studies have provided new perspectives on the molecular biology, ontogeny and classification of ENKTL and further identified dysregulated signaling pathways such as Janus associated kinase (/Signal Transducer and activation of transcription (JAK/STAT), Platelet derived growth factor (PDGF), Aurora Kinase and NF-κB, which are under evaluation as therapeutic targets. Copy number analyses have highlighted potential tumor suppressor genes such as PR Domain Zinc Finger Protein 1 (PRDM1) and protein tyrosine phosphatase kappa (PTPRK) while next generation sequencing studies have identified recurrently mutated genes in pro-survival and anti-apoptotic pathways. The discovery of epigenetic dysregulation and aberrant microRNA activity has broadened our understanding of the biology of ENKTL. Importantly, immunotherapy via Programmed Cell Death -1 (PD-1) and Programmed Cell Death Ligand1 (PD-L1) checkpoint signaling inhibition is emerging as an attractive therapeutic strategy in ENKTL. Herein, we present an overview of the molecular biology and genomic landscape of ENKTL with a focus on the most promising translational opportunities.

【 授权许可】

Unknown