Heavy Light Chain in Chronic Lymphocytic Leukemia

Analysis of immunoglobulin heavy/light chain pairs In chronic lymphocytic leukemia

Introduction and Background:

Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia in the western world. Median age at diagnosis is 72 years, and the male to female ratio is 2:1. The disease is characterized by an accumulation of monoclonal mature B-cells which co-express the T-cell antigen CD5, B-cell surface antigens CD19, CD20, and CD23(1) and either kappa or lambda immunoglobulin light chains restriction (2). Diagnosis is established based on the IWCLL criteria published by Hallek at al in 2008. (1).

CLL may have a heterogeneous clinical course with a wide spectrum of manifestations ranging from long lived asymptomatic patients who never require treatment to those with a more rapid clinical course and symptomatic progression. One of the remaining important challenges in CLL is to stratify patients into different prognostic categories, so as to plan appropriate targeted therapy when necessary . The most important prognostic factor in CLL relates to the presence of typical genomic aberrations in the leukemic cell (3). Other essential prognostic parameters include: CD38 expression, the presence of ZAP-70, immunoglobulin heavy chain mutational status, and beta 2 microglobulin (B2MG) levels. (1).

Patients with CLL, have a 10 % risk of developing autoimmune complications mostly auto-immune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) (4-6). The pathogenesis for these autoimmune cytopenias is linked to the production of polyclonal immunoglobulin G (IgG) antibodies (less frequently IgM) directed against a variety of red blood cell or platelet antigens. (4-6).