Natural-killer/T cell
lymphoma (NKTCL) represents the most common subtype of extranodal
lymphoma with aggressive clinical behavior. Prevalent in Asians and South Americans, the pathogenesis of NKTCL remains to be fully elucidated. Using system biology techniques including genomics, transcriptomics, epigenomics, and metabolomics, novel
biomarkers and therapeutic targets have been revealed in NKTCL. Whole-exome sequencing studies identify recurrent somatic gene mutations, involving
RNA helicases,
tumor suppressors, JAK-STAT pathway molecules, and epigenetic modifiers. Another genome-wide association study reports that single nucleotide polymorphisms mapping to the class II MHC region on chromosome 6 contribute to lymphomagenesis. Alterations of oncogenic signaling pathways
janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-κB (NF-κB),
mitogen-activated protein kinase (MAPK), WNT, and NOTCH, as well as epigenetic dysregulation of
microRNA and long non-coding RNAs, are also frequently observed in NKTCL. As for metabolomic profiling, abnormal
amino acids metabolism plays an important role on
disease progression of NKTCL. Of note, through targeting multiple omics aberrations, clinical outcome of NKTCL patients has been significantly improved by
asparaginase-based regimens, immune checkpoints inhibitors, and
histone deacetylation inhibitors. Future investigations will be emphasized on molecular classification of NKTCL using integrated analysis of system biology, so as to optimize targeted therapeutic strategies of NKTCL in the era of
precision medicine.