Proliférations chroniques à grands lymphocytes granuleux. Aspects cliniques et pathogéniques

Abstract

Introduction. – The clinical course, biological features, and recent data on the pathogenesis of large granular lymphocyte (LGL) leukemia are reviewed. Current knowledge and key points. – Clonal diseases of LGL disorders can arise from a CD3+, CD57+ T-cell lineage, which are the most frequent, or from a CD3-, CD56+ NK-cell lineage. The diagnosis of LGL leukemia is suspected on the basis of a persistent excess of LGL, usually with neutropenia and splenomegaly. It is assessed by immunophenotypic and molecular studies of T-cell receptor clonality (southern blot, PCR). Association with autoimmune diseases (rheumatoid arthritis, erythroblastopenia, etc.) is a main feature of chronic LGL proliferation. Questions about a viral agent (HTLV1?), facilitation of clonal expansion by cytokines (IL-12, IL-15), and the defective Fas apoptotic pathway are discussed. Treatment of symptomatic LGL proliferations is based on immunosuppressive agents (principally methotrexate and cyclophosphamide). Future prospect and projects. – The epidemiology, prognosis factors, therapeutics and the pathogenesis of LGL leukemia are unknown. We proposed the creation of a French register of LGL expansions to explore these different aspects.