METHODS FOR STRATIFICATION AND TREATMENT OF A PATIENT SUFFERING FROM CHRONIC LYMPHOCYTIC LEUKEMIA

摘要

The present invention relates to methods for stratification and treatment of progressive chronic lymphocytic in a patient in need thereof Depending on the cytokines produced, several regulatory B cell (Breg) subsets contribute to immune resolution and their enrichment leads to disease-associated immunosuppression. Chronic Lymphocytic Leukemia (CLL) is a heterogeneous clonal B cell neoplasm ranging from indolent to rapidly progressive clinical course that eludes tumor clearance. This study presents a comprehensive phenotypic and functional analysis of the regulatory subpopulations in CLL patients at various stages of the disease. Cytokines profiling of CLL-B cells evidences the production at various extents of IL-10 and TGFβ1. Remarkably, CLL cells express also the FOXP3 transcription factor, an original marker of regulatory T cells. The three proteins are produced by subpopulations with markers of activated and memory Β cells defining a specific signature. Based on CD5 and CD19 expression, intraclonal heterogeneity showed differential regulatory factors production relevant to disease evolution. Functional studies proved their regulatory capacities targeting T cell differentiation, proliferation and secretion. IL-10, TGFβ1 and FOXP3 expressions combined in a polyfunctional score strongly correlated with high-risk factors of progression. This profiling helps to predict progression and pinpoints immune dysfunction in CLL. Thus, the present invention relates to methods for diagnosing progressive chronic lymphocytic in a patient comprising a step of determining the level of IL-10, TGFβ1 and FOXP3 and methods for treating said patient.