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

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.