title: Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma.
abstract: Natural killer/T-cell lymphoma (NKTCL) is a rare, aggressive form of non-Hodgkin lymphoma that is generally incurable at more advanced stages with systemic involvement. Clonal diagnostic markers (eg, unique T- or B-cell receptor rearrangements) are not available for NKTCLs. Killer cell immunoglobulin like receptors (KIRs) are a family of type I transmembrane glycoproteins involved in the inhibition or activation of NK cells. A restricted expression profile of KIRs has been proposed as clonal markers of NK-cell proliferations. Here we evaluated the transcription profile of all KIR family genes and C-type lectin receptor genes using RNA sequencing on NKTCL cases (n = 17) and NK-cell lines (n = 3). The expression of all KIRs tended to be markedly reduced or absent in NKTCL, except for the KIR family member killer Ig-like receptor 2DL4 (KIR2DL4; alias CD158D), which was selectively overexpressed in the majority (59%) of cases. No specific expression pattern was observed for C-type lectin receptors. KIR2DL4 is an unusual member of the KIR family that recognizes human leukocyte antigen G and mediates NK-cell activation through inducing proliferation and survival pathways such as AKT and NF-κB. Stable knockdown of KIR2DL4 in two malignant NK-cell lines with high KIR2DL4 expression significantly reduced cell growth. Selective overexpression of KIR2DL4 and down-regulation of inhibitory KIRs may contribute to NKTCL pathogenesis.
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California; İzmir International Biomedicine and Genome Institute (iBG-İzmir), Dokuz Eylul University, İzmir, Turkey; Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey. Electronic address: can.kucuk@deu.edu.tr.
authors.forename: Can
authors.initials: C
authors.lastname: Küçük
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California; İzmir International Biomedicine and Genome Institute (iBG-İzmir), Dokuz Eylul University, İzmir, Turkey.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gong
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California.
authors.forename: Bei
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Adam
authors.initials: A
authors.lastname: Cornish
authors.affiliation: Department of Pathology, Groupe Henri-Mondor Albert-Chenevier, Inserm U955, Université Paris Est, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California.
authors.forename: Timothy
authors.initials: T
authors.lastname: McKeithan
authors.affiliation: Department of Pathology, City of Hope Medical Center, Duarte, California. Electronic address: jochan@coh.org.
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054340:Receptors, KIR / Q000032:analysis / Q000096:biosynthesis*; D059467:Transcriptome; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D054340:Receptors, KIR