P594: Increased Frequencies of Igh Locus Suicide Recombination Points on Chronic Lymphocytic Leukemia With Low Rate of Aid Related Somatic Mutations, Myc Overexpression and Short Telomeres

Abstract

Background: Background:In normal B-cells, Activation Induced-cytidine deaminase (AID) is the key enzyme for class switch recombination (CSR) and IGHV somatic hypermutation (SHM). AID is also implicated in another IgH rearrangement, the Locus Suicide Recombination (LSR). LSR occurs in activated B-cells and recombines the IgH locus between the switch µ (Sµ) region and one 3'a2 regulatory region (3'a2RR) of the IgH locus. LSR results in the complete deletion of the cluster of IgH constant genes. When LSR hits the active IgH locus, it induces the loss of BCR expression and the death of the concerned B cell. Chronic lymphocytic leukemia (CLL) is an indolent non-Hodgkin B-cell lymphoma. Tumor CLL B-cells weakly express a B cell receptor (BCR) on the surface which is composed, in the vast majority of cases, of immunoglobulins (Ig) of the mu (µ) and delta (δ ) isotypes and Ig class-switched CLL are rare, raising the question of abnormalities in the Ig gene recombination machinery in this B-cell cancer.