Analysis of immunoglobulin heavy variable chain rearrangement in chronic lymphocytic leukemia patients among Chornobyl clean-up workers.

Abstract

A number of epidemiological studies have shown an elevated radiation-associated risk for chronic lymphocytic leukemia(CLL). The aim of the paper was to analyze immunoglobulin heavy variable chain (IGHV) rearrangement and IGHV usage in CLL cases associated with ionizing radiation (IR) exposure. Samples of 76clean-up workers of Chornobyl Nuclear Power Plant accident of 1986 (the main group) and 194non-exposed patients (the control group) were analyzed. Two groups of CLL patients were comparable by gender (all patients were male), age, and place of residence (rural or urban). Some features of IR-associated CLL cases as compared to CLL cases in patients without history of IR exposure were revealed. Among unmutated IGHV sequences, IGHV1genes were less commonly used (29.4% vs 48.6%; p= 0.018), while the frequency of IGHD6genes was higher (23.5% vs 10%; p= 0.029). The unmutated IGHV sequences did not use IGHD3-16gene (0% vs 7.9%, p= 0.038). Mutated IGHV sequences were less frequently expressed IGHV3genes (44% vs 68.5%; p= 0.037) due low representation of IGHV3-21 (4% vs 11.1%) and IGHV3-23 (0% vs 11.1%) genes; did not use IGHD3-22gene (0% vs 18.5%, p= 0.025); and have signs of positive selection in the HCDR regions (Σ= 0.5029± 0.155vs -0.0539± 0.14; p= 0.013). The revealed differences in IGHV gene usage and B-cell receptor structure in the main and the control groups of CLL patients indirectly indicate a change in the spectrum of antigens associated with CLL under IR exposure. The possible antigenic drivers associated with CLL associated with IR exposure are discussed.