Natasha E Lewis1, Qi Gao1, Kseniya Petrova-Drus1,2, Melissa Pulitzer3, Allison Sigler1, Jeeyeon Baik1, Alison J Moskowitz4, Steven M Horwitz4, Ahmet Dogan1, Mikhail Roshal1. 1. Hematopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 2. Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 3. Dermatopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 4. Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Abstract
BACKGROUND: Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry. METHODS: 50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases. RESULTS: Normal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients. CONCLUSIONS: PD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.
BACKGROUND: Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death-1 (PD-1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry. METHODS: 50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD-1 was assessed over time in blood and bone marrow of available MF/SS cases. RESULTS: Normal CD4+ T cells showed dim/intermediate to absent PD-1 expression. PD-1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD-1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD-1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan-T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD-1 remained informative in blood/bone marrow over time in most patients. CONCLUSIONS: PD-1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.
Authors: Rein Willemze; Lorenzo Cerroni; Werner Kempf; Emilio Berti; Fabio Facchetti; Steven H Swerdlow; Elaine S Jaffe Journal: Blood Date: 2019-01-11 Impact factor: 22.113
Authors: Pedro Horna; Darcie M Deaver; Dahui Qin; Lynn C Moscinski; Eduardo M Sotomayor; L Frank Glass; Lubomir Sokol Journal: J Clin Pathol Date: 2013-12-06 Impact factor: 3.411
Authors: Sara Samimi; Bernice Benoit; Katherine Evans; E John Wherry; Louise Showe; Maria Wysocka; Alain H Rook Journal: Arch Dermatol Date: 2010-08-16
Authors: A W Langerak; P J T A Groenen; M Brüggemann; K Beldjord; C Bellan; L Bonello; E Boone; G I Carter; M Catherwood; F Davi; M-H Delfau-Larue; T Diss; P A S Evans; P Gameiro; R Garcia Sanz; D Gonzalez; D Grand; A Håkansson; M Hummel; H Liu; L Lombardia; E A Macintyre; B J Milner; S Montes-Moreno; E Schuuring; M Spaargaren; E Hodges; J J M van Dongen Journal: Leukemia Date: 2012-08-24 Impact factor: 11.528
Authors: Jil M Jubel; Zachary R Barbati; Christof Burger; Dieter C Wirtz; Frank A Schildberg Journal: Front Immunol Date: 2020-03-24 Impact factor: 7.561