Naïve/memory T-cell phenotypes in leukemic cutaneous T-cell lymphoma: Putative cell of origin overlaps disease classification

Pedro Horna, Lynn C. Moscinski, Lubomir Sokol, Haipeng Shao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Mycosis fungoides (MF) and Sézary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. Methods: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as naïve (TN), central memory (TCM), effector memory (TEM), or effector memory with reacquired CD45RA (TEMRA); based on CD62L+/CD45RA+, CD62L+/CD45RA, CD62L/CD45RA, or CD62L/CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. Results: The naïve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN, TCM, TEM, or TEMRA subset on 11 (14%), 32 (41%), 30 (38%), and 6 (8%) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The naïve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the naïve/memory phenotype was different from the original phenotype. Conclusions: Both SS and MF can have phenotypic features of any of the major naïve/memory T-cell subsets, which questions the current principle of “cell-of-origin” distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalCytometry Part B - Clinical Cytometry
Volume96
Issue number3
DOIs
StatePublished - May 1 2019

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Cutaneous T-Cell Lymphoma
Mycosis Fungoides
T-Lymphocytes
Phenotype
Differentiation Antigens
T-Lymphocyte Subsets
Flow Cytometry
Color
Bone Marrow
Neoplasms

Keywords

  • flow cytometry
  • memory T-cells
  • mycosis fungoides
  • naïve T-cells
  • Sézary syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Naïve/memory T-cell phenotypes in leukemic cutaneous T-cell lymphoma : Putative cell of origin overlaps disease classification. / Horna, Pedro; Moscinski, Lynn C.; Sokol, Lubomir; Shao, Haipeng.

In: Cytometry Part B - Clinical Cytometry, Vol. 96, No. 3, 01.05.2019, p. 234-241.

Research output: Contribution to journalArticle

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title = "Na{\"i}ve/memory T-cell phenotypes in leukemic cutaneous T-cell lymphoma: Putative cell of origin overlaps disease classification",
abstract = "Background: Mycosis fungoides (MF) and S{\'e}zary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. Methods: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as na{\"i}ve (TN), central memory (TCM), effector memory (TEM), or effector memory with reacquired CD45RA (TEMRA); based on CD62L+/CD45RA+, CD62L+/CD45RA−, CD62L−/CD45RA−, or CD62L−/CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. Results: The na{\"i}ve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN, TCM, TEM, or TEMRA subset on 11 (14{\%}), 32 (41{\%}), 30 (38{\%}), and 6 (8{\%}) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The na{\"i}ve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the na{\"i}ve/memory phenotype was different from the original phenotype. Conclusions: Both SS and MF can have phenotypic features of any of the major na{\"i}ve/memory T-cell subsets, which questions the current principle of “cell-of-origin” distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.",
keywords = "flow cytometry, memory T-cells, mycosis fungoides, na{\"i}ve T-cells, S{\'e}zary syndrome",
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T1 - Naïve/memory T-cell phenotypes in leukemic cutaneous T-cell lymphoma

T2 - Putative cell of origin overlaps disease classification

AU - Horna, Pedro

AU - Moscinski, Lynn C.

AU - Sokol, Lubomir

AU - Shao, Haipeng

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Mycosis fungoides (MF) and Sézary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. Methods: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as naïve (TN), central memory (TCM), effector memory (TEM), or effector memory with reacquired CD45RA (TEMRA); based on CD62L+/CD45RA+, CD62L+/CD45RA−, CD62L−/CD45RA−, or CD62L−/CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. Results: The naïve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN, TCM, TEM, or TEMRA subset on 11 (14%), 32 (41%), 30 (38%), and 6 (8%) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The naïve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the naïve/memory phenotype was different from the original phenotype. Conclusions: Both SS and MF can have phenotypic features of any of the major naïve/memory T-cell subsets, which questions the current principle of “cell-of-origin” distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.

AB - Background: Mycosis fungoides (MF) and Sézary Syndrome (SS) are clinically distinct cutaneous T-cell lymphomas with strikingly similar morphologic and phenotypic features. Prior studies have suggested phenotypic differences based on markers of antigen experience, suggesting a different cell of origin. Methods: Seventy-nine involved peripheral blood or bone marrow samples from 33 patients with SS and 19 patients with MF were studied by 10-color flow cytometry, including CD62L, CD45RA, CCR4, and PD-1. Gated tumor events were classified as naïve (TN), central memory (TCM), effector memory (TEM), or effector memory with reacquired CD45RA (TEMRA); based on CD62L+/CD45RA+, CD62L+/CD45RA−, CD62L−/CD45RA−, or CD62L−/CD45RA+ phenotype, respectively. Sequential specimens were compared to assess for phenotypic stability. Results: The naïve/memory phenotype of the neoplastic T-cells was markedly heterogeneous, with a dominant TN, TCM, TEM, or TEMRA subset on 11 (14%), 32 (41%), 30 (38%), and 6 (8%) cases, respectively. There was no correlation between the diagnosis of MF or SS and putative cell of origin (P = 0.4). Overexpression of CCR4 and PD1 was observed in most cases, with higher intensity in SS compared to MF. The naïve/memory phenotype remained the same for 10 patients up to 273 days after the initial analysis; while on six patients, the naïve/memory phenotype was different from the original phenotype. Conclusions: Both SS and MF can have phenotypic features of any of the major naïve/memory T-cell subsets, which questions the current principle of “cell-of-origin” distinction between SS and MF. Phenotypic shifts within these subsets are common, suggesting a functional state rather than a cell-of-origin surrogate.

KW - flow cytometry

KW - memory T-cells

KW - mycosis fungoides

KW - naïve T-cells

KW - Sézary syndrome

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