Risk stratification of adult T-cell leukemia/lymphoma using immunophenotyping
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文摘
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 CD4p>+p> CCR4p>+p> CD26p>−p> immunophenotype and the frequency of CD4p>+p> CCR4p>+p> CD26p>−p> T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4p>+p> CCR4p>+p> CD26p>−p> as a marker of HTLV-1-infected cells. Further immunophenotyping of CD4p>+p> CCR4p>+p> CD26p>−p> cells revealed that 95% patients with ATL had a CD7p>−p> (≤30% CD7p>+p> cells), whereas 95% HTLV+ non-ATL had CD7p>+p> (>30% CD7p>+p> cells) immunophenotype. All patients with aggressive ATL had a CCR7p>+p> (≥30%), whereas 92% with indolent ATL and 100% non-ATL had a CCR7p>−p> (<30%) immunophenotype. Patients with nonprogressing indolent ATL were CD127p>+p> but those with progressive lymphocytosis requiring systemic therapy had a CD127p>−p> (≤30%) immunophenotype. In summary, HTLV-1-infected cells have a CD4p>+p> CCR4p>+p> CD26p>−p> immunophenotype. Within this population, CD7p>−p> phenotype suggests a diagnosis of ATL, CCR7p>+p> phenotype identifies aggressive ATL, while CCR7p>−p> CD127p>−p> phenotype identifies progressive indolent ATL.

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