Aberrations of the immunoglobulin heavy chain locus in patients with chronic lymphocytic leukemia detected with fluorescence in situ hybridization

Abstract

Background. Genetic disorders play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Identification of these disorders can be used for prognosis of the disease. This is an urgent task since the clinical course of CLL is extremely heterogeneous. The aim of this study was to explore cytogenetic aberrations of the immunoglobulin heavy chain (IGH) locus and their association with a common FISH panel in patients with chronic lymphocytic leukemia (CLL).
Materials and methods. The study was performed by a retrospective analysis of samples of non-stimulated lymphocytes from 89 patients with newly diagnosed CLL and 15 clinically healthy donors as a control group using interphase fluorescence in situ hybridization (I-FISH).
Results. Rearrangements of the IGH locus were found in 64% of CLL patients. IGH translocations were observed in 19% of patients whereas 58% of patients had total or partial IGHV deletions. The patients were divided into three groups and evaluated for occurrence of aberrations in the locus 14q32. The group of unfavorable prognosis included 35 patients (16 patients with del17p13 and 19 patients with del11q22); the group of intermediate prognosis included 18 patients (10 patients with chromosome 12 trisomy and 8 patients without identified aberrations); and the group of favorable prognosis consisted of 36 patients with del13q14 as the sole abnormality. There were no statistically significant differences between groups with different prognosis in the occurrence of patients with IGH translocations. IGHV deletions were significantly more frequent in patients with del17p13 and del11q22 than in patients with del13q14 as the sole abnormality (74% vs. 44%, p=0.011). Patients with a high (50% and more) proportion of cells with IGHV deletions occurred approximately 4 times more frequently in groups of unfavorable and intermediate prognosis compared to the group of favorable prognosis (40% and 39% vs. 11%, respectively, p<0.05).
Conclusion. Rearrangements of the IGH locus detected using the FISH method is the second among all aberrations in CLL. These abnormalities may be important as they are significantly more frequently observed in patients with an unfavorable prognosis. Further observation of CLL patients with IGH aberrations will allow to identify clinical and biological features and prognostic importance of these aberrations. Probably, the intergroup heterogeneity of the clinical course in patients with a favorable prognosis determined on a hierarchical model is due to additional cytogenetic aberrations including IGH locus abnormalities.