Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 186, Issue 6, Pages 1435-1441Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.02.011
Keywords
-
Categories
Funding
- NIH Lymphoma Specialized Programs of Research Excellence grant [P50CA136411-01]
- Science Academy's Young Scientist Awards Program (BAGEP)
- Scientific and Technological Research Council of Turkey (TUBITAK) 2232 [115C006]
- National Cancer Institute of the NIH award [P30CA033572, P50CA107399]
- National Center for Research Resources [1S10RR027754-01, 5P20RR016469, RR018788-08]
- National Institute for General Medical Science [8P20GM103427, GM103471-09]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available