PMID- 37385341
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20230908
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 36
IP  - 8
DP  - 2023 Aug
TI  - Establishing NK-Cell Receptor Restriction by Flow Cytometry and Detecting 
      Potential NK-Cell Clones of Uncertain Significance.
PG  - 100255
LID - S0893-3952(23)00160-6 [pii]
LID - 10.1016/j.modpat.2023.100255 [doi]
AB  - Natural killer (NK) cells develop a complex inhibitory and/or activating NK-cell 
      receptor system, including killer cell immunoglobulin-like receptors (KIRs or 
      CD158) and CD94/NKG2 dimers, which are variably combined to generate the 
      individual's NK-cell receptor repertoire. Establishing NK-cell receptor 
      restriction by flow cytometric immunophenotyping is an important step in 
      diagnosing NK-cell neoplasms, but reference interval (RI) data for interpreting 
      these studies are lacking. Specimens from 145 donors and 63 patients with NK-cell 
      neoplasms were used to identify discriminatory rules based on 95% and 99% 
      nonparametric RIs for CD158a+, CD158b+, CD158e+, KIR-negative, and NKG2A+ NK-cell 
      populations to establish NK-cell receptor restriction. These 99% upper RI limits 
      (NKG2a >88% or CD158a >53% or CD158b >72% or CD158e >54% or KIR-negative >72%) 
      provided optimal discrimination between NK-cell neoplasm cases and healthy donor 
      controls with an accuracy of 100% compared with the clinicopathologic diagnosis. 
      The selected rules were applied to 62 consecutive samples received in our flow 
      cytometry laboratory that were reflexed to an NK-cell panel due to an expanded 
      NK-cell percentage (exceeding 40% of total lymphocytes). Twenty-two (35%) of 62 
      samples were found to harbor a very small NK-cell population with restricted 
      NK-cell receptor expression based on the rule combination, suggestive of NK-cell 
      clonality. A thorough clinicopathologic evaluation for the 62 patients did not 
      reveal diagnostic features of NK-cell neoplasms; therefore, these potential 
      clonal populations of NK cells were designated as NK-cell clones of uncertain 
      significance (NK-CUS). In this study, we established decision rules for NK-cell 
      receptor restriction from the largest published cohorts of healthy donors and 
      NK-cell neoplasms. The presence of small NK-cell populations with restricted 
      NK-cell receptors does not appear to be an uncommon finding, and its significance 
      requires further exploration.
CI  - Copyright (c) 2023 United States & Canadian Academy of Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Seheult, Jansen N
AU  - Seheult JN
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Otteson, Gregory E
AU  - Otteson GE
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Jevremovic, Dragan
AU  - Jevremovic D
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Horna, Pedro
AU  - Horna P
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Timm, Michael M
AU  - Timm MM
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Yuan, Ji
AU  - Yuan J
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Morice, William G
AU  - Morice WG
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Olteanu, Horatiu
AU  - Olteanu H
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota.
FAU - Shi, Min
AU  - Shi M
AD  - Division of Hematopathology, Department of Laboratory Medicine and Pathology, 
      Mayo Clinic, Rochester, Minnesota. Electronic address: Shi.Min@mayo.edu.
LA  - eng
PT  - Journal Article
DEP - 20230628
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Humans
MH  - Receptors, Natural Killer Cell/metabolism
MH  - Flow Cytometry
MH  - *Killer Cells, Natural/metabolism
MH  - *Receptors, KIR/metabolism
MH  - Clone Cells
OTO - NOTNLM
OT  - NK-cell clones of uncertain significance
OT  - NK-cell receptor restriction
OT  - flow cytometry
EDAT- 2023/06/30 01:06
MHDA- 2023/08/21 06:43
CRDT- 2023/06/29 19:13
PHST- 2023/03/29 00:00 [received]
PHST- 2023/06/13 00:00 [revised]
PHST- 2023/06/14 00:00 [accepted]
PHST- 2023/08/21 06:43 [medline]
PHST- 2023/06/30 01:06 [pubmed]
PHST- 2023/06/29 19:13 [entrez]
AID - S0893-3952(23)00160-6 [pii]
AID - 10.1016/j.modpat.2023.100255 [doi]
PST - ppublish
SO  - Mod Pathol. 2023 Aug;36(8):100255. doi: 10.1016/j.modpat.2023.100255. Epub 2023 
      Jun 28.