Restricted Killer Cell Immunoglobulin-Like Receptor Repertoire without T-Cell Receptor γ Rearrangement Supports a True Natural Killer-Cell Lineage in a Subset of Sinonasal Lymphomas

Abstract

The cellular lineage of sinonasal T/NK (natural killer) cell lymphoma remains controversial. Lineage assignment is difficult because T cells and NK cells have a similar morphology and surface markers. Consequently, the assignment must depend heavily on the status of T-cell receptor (TCR) rearrangement. A monoclonal TCR rearrangement supports a T lineage; however, a corresponding monoclonality test for NK cells has not yet been established. Each NK cell bears a distinct set of killer cell immunoglobulin (Ig)-like receptors (KIRs) that are randomly distributed over three groups. In principle, restriction of the KIR repertoire signifies a monoclonal or possibly oligoclonal NK-cell proliferation, just as Ig light-chain restriction usually indicates a monoclonal B-cell neoplasm. Using a novel group-specific reverse transcriptase-polymerase chain reaction, we found a restricted KIR repertoire in most sinonasal lymphomas (9 of 10), but only rarely in T-cell lymphomas (2 of 10) or reactive conditions involving T/NK cells (1 of 10). KIR+ sinonasal lymphomas usually lacked a monoclonal TCR-gamma rearrangement pattern, expressed another NK cell receptor, NKG2a, and were usually CD56-positve, cyclin-dependent kinase-6 (CDK6)-positive, CD44-negative, a phenotype already reported to indicate a true NK cell lineage. We conclude that, although sinonasal lymphomas have heterogeneous genotypes and phenotypes, a restricted KIR repertoire without TCR-gamma rearrangement provides preliminary support for the monoclonality hypothesis and can be used for defining a true NK-cell lineage in a subset of sinonasal lymphomas.

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

“…In addition, specific and exclusive expression of a single KIR family gene member, KIR2DL4, was observed, which suggests a possible oncogenic role for it during the transformation of NK cells. This observation is consistent but more extreme than previous reports showing dominant expression of KIR2DL4 in NKTCL cases using other methodologies such as DNA microarray, 4 RT-PCR, 24 or flow cytometry. 25 This difference using different methodologies for quantification of expression may be due to the following reasons: KIR mRNA sequences are highly similar, and DNA microarray probe sets are not as specific as RNA-seq for the measurement of the expression of individual KIR genes.…”

Presence of Restricted Killer Immunoglobulin-Like Receptor Repertoire and Monoclonal T-Cell Receptor γ Rearrangement as Evidence of Mixed NK/T-Cell Differentiation in a Subset of Sinonasal Lymphomas

“…These receptors were randomly distributed over three alternative splicing groups in a polyclonal NK-cell population, but were restricted to one or two groups in SNLs. Thus, a restricted KIR repertoire (r-KIR ϩ ) without a monoclonal TCR rearrangement (r-TCR Ϫ ) in the majority (approximately 60%) of SNLs further confirms their origin from the true NK lineage (Lin et al, 2001).…”

“…Because these clonotypical receptors are randomly distributed, a reactive condition involving polyclonal NK cells would have an unrestricted KIR repertoire of all three groups. Conversely, a KIR repertoire restricted to one or two of the three groups would signify an NK-cell lymphoma (Lin et al, 2001). A typical result of the KIR repertoire analysis is shown in Figure 1.…”

“…We used a reverse transcription-polymerase chain reaction (RT-PCR) approach for analysis of KIRs (Lin et al, 2001). These receptors have a consensus sequence composed of three Ig-like domains, and can be divided into three groups due to alternative splicing.…”

Aspects moléculaires des lymphomes T périphériques (2)

“…Gènes candidats dans la région 6q21-6q25 La délétion la plus fréquente, qui concerne le bras long du chromosome 6 (6q21-6q25), est retrouvée dans 40 à [5]. Néanmoins, dans un tiers des cas, les cellules tumorales ont des marqueurs de surface et des profils transcriptomiques de lymphocytes T cytotoxiques, le plus souvent [6,7].…”