Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping

Huseini H. Kagdi, Maria A. Demontis, Paul A. Fields, Juan Carlos Ramos, Charles R M Bangham, Graham P. Taylor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Adult T-cell leukemia/lymphoma (ATL), a human T-lymphotropic virus type 1 (HTLV-1)-associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from 10 HTLV-1-uninfected subjects (UI), 54 HTLV-1-infected patients with non-ATL, and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4+ CCR4+ CD26 immunophenotype and the frequency of CD4+ CCR4+ CD26 T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4+ CCR4+ CD26 as a marker of HTLV-1-infected cells. Further immunophenotyping of CD4+ CCR4+ CD26 cells revealed that 95% patients with ATL had a CD7 (≤30% CD7+ cells), whereas 95% HTLV+ non-ATL had CD7+ (>30% CD7+ cells) immunophenotype. All patients with aggressive ATL had a CCR7+ (≥30%), whereas 92% with indolent ATL and 100% non-ATL had a CCR7 (<30%) immunophenotype. Patients with nonprogressing indolent ATL were CD127+ but those with progressive lymphocytosis requiring systemic therapy had a CD127 (≤30%) immunophenotype. In summary, HTLV-1-infected cells have a CD4+ CCR4+ CD26 immunophenotype. Within this population, CD7 phenotype suggests a diagnosis of ATL, CCR7+ phenotype identifies aggressive ATL, while CCR7 CD127 phenotype identifies progressive indolent ATL.

Original languageEnglish (US)
Pages (from-to)298-309
Number of pages12
JournalCancer Medicine
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2017

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Immunophenotyping
Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
T-Cell Leukemia
T-Cell Lymphoma
Phenotype
Lymphocytosis
Virus Diseases

Keywords

  • Adult T-cell leukemia/lymphoma (ATL)
  • chemokine receptor(s)
  • human T-lymphotropic virus type 1 (HTLV-1)
  • immunophenotyping
  • interleukin receptor(s)

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Kagdi, H. H., Demontis, M. A., Fields, P. A., Carlos Ramos, J., Bangham, C. R. M., & Taylor, G. P. (2017). Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping. Cancer Medicine, 6(1), 298-309. https://doi.org/10.1002/cam4.928

Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping. / Kagdi, Huseini H.; Demontis, Maria A.; Fields, Paul A.; Carlos Ramos, Juan; Bangham, Charles R M; Taylor, Graham P.

In: Cancer Medicine, Vol. 6, No. 1, 01.01.2017, p. 298-309.

Research output: Contribution to journalArticle

Kagdi, HH, Demontis, MA, Fields, PA, Carlos Ramos, J, Bangham, CRM & Taylor, GP 2017, 'Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping', Cancer Medicine, vol. 6, no. 1, pp. 298-309. https://doi.org/10.1002/cam4.928
Kagdi, Huseini H. ; Demontis, Maria A. ; Fields, Paul A. ; Carlos Ramos, Juan ; Bangham, Charles R M ; Taylor, Graham P. / Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping. In: Cancer Medicine. 2017 ; Vol. 6, No. 1. pp. 298-309.
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abstract = "Adult T-cell leukemia/lymphoma (ATL), a human T-lymphotropic virus type 1 (HTLV-1)-associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and nonmalignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL, we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from 10 HTLV-1-uninfected subjects (UI), 54 HTLV-1-infected patients with non-ATL, and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4+ CCR4+ CD26− immunophenotype and the frequency of CD4+ CCR4+ CD26− T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4+ CCR4+ CD26− as a marker of HTLV-1-infected cells. Further immunophenotyping of CD4+ CCR4+ CD26− cells revealed that 95{\%} patients with ATL had a CD7− (≤30{\%} CD7+ cells), whereas 95{\%} HTLV+ non-ATL had CD7+ (>30{\%} CD7+ cells) immunophenotype. All patients with aggressive ATL had a CCR7+ (≥30{\%}), whereas 92{\%} with indolent ATL and 100{\%} non-ATL had a CCR7− (<30{\%}) immunophenotype. Patients with nonprogressing indolent ATL were CD127+ but those with progressive lymphocytosis requiring systemic therapy had a CD127− (≤30{\%}) immunophenotype. In summary, HTLV-1-infected cells have a CD4+ CCR4+ CD26− immunophenotype. Within this population, CD7− phenotype suggests a diagnosis of ATL, CCR7+ phenotype identifies aggressive ATL, while CCR7− CD127− phenotype identifies progressive indolent ATL.",
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