title: Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping.
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.
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, UK.
authors.forename: Huseini H
authors.initials: HH
authors.lastname: Kagdi
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, UK.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Demontis
authors.affiliation: Department of Hematology, Guys Hospital, London, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fields
authors.affiliation: Department of Hematology/Oncology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, UK.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000378:metabolism; D003937:Diagnosis, Differential; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005260:Female; D015490:HTLV-I Infections / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054398:Receptors, CCR4 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: C515354:CCR4 protein, human; D015704:CD4 Antigens; D054398:Receptors, CCR4; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Adult T-cell leukemia/lymphoma (ATL); chemokine receptor(s); human T-lymphotropic virus type 1 (HTLV-1); immunophenotyping; interleukin receptor(s)