Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

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KÜÇÜK C., Hu X., Gong Q., Jiang B., Cornish A., Gaulard P., ...More

AMERICAN JOURNAL OF PATHOLOGY, vol.186, no.6, pp.1435-1441, 2016 (SCI-Expanded, Scopus)

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-kappa B. 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.