Development And Validation Of A New Tool For The Characterization Of Immunoglobulin Gene Rearrangements In Patients With Chronic Lymphocytic Leukemia By Deep Next Generation Sequencing

Introduction: Chronic Lymphocytic Leukemia (CLL) is a deeply heterogeneous disease from both biological and clinical points of view. This heterogeneity is partly reflected by differences in the mutation status of immunoglobulin variable heavy chain (IgHV) genes. According to this criterion, two main subsets are distinguished by whether CLL cells express an unmutated or mutated, reflecting the stage of normal B cell differentiation from which they originate. These groups also have important clinical differences in terms of clinical outcome. Thus, patients with unmutated IgHV (UM; ≥98% of identity to the germline) genes have a more aggressive disease course and develop more frequently unfavourable genetic deletions or mutations than patients with mutated IgHV (M; <98%).