Authors: V. Kuhrová 1; H. Francová 1; D. Klimešová 1; Y. Brychtová 2; M. Doubek 2; M. Trbušek 1; M. Brejcha 3; D. Dvořáková 1; J. Mayer 1,2 Authors‘ workplace: Centrum molekulární biologie a genové terapie FN, Brno 1; Interní hematoonkologická klinika FN, Brno 2; PaR LAB s. r. o., onkohematologická ambulance, Nový Jičín 3 Published in: Čas. Lék. čes. 2006; 145: 855-858 Category: Original Article
Background. Chronic lymphocytic leukemia is a heterogeneous disease manifesting with a variable clinical course. It is evident from many studies, that the division into two main prognostic categories is possible on the basis of mutation status of the immunoglobulin heavy-chain gene. The objective of our work was to identify a presence or absence of IgVH gene mutations in B-CLL patients which are monitored or treated on hematological clinics and to determine the presence of individual D and JH subgenes in malignant population of B-cells.
Methods and Results. A nucleotide sequence of IgVH gene of neoplastic cells was analyzed by appropriate molecular-genetic methods. RNA/cDNA was collected from 358 patients and a spectrum of individual subgenes translocations was identified. Our results show that 56.3% of patients manifested an unmutated variable (VH) segment. It is expected from the published data that this group of patients will suffer from aggressive course of the disease and will exhibit a substantially shorter survival in comparison to patients possessing somatic hypermutations. An expanded population of leukemic B-cells showed increased occurrence of clones whose variable segments belong to three different families. VH3 alleles are the ones most frequently used. A frequency of unmutated alleles is prominently shifted into families with VH1 homology. The preferred „diversity and joining“ segments are D3, D2 and JH 4 and JH 6.
Conclusions. The analysis of heavy chain immunoglobulin gene after recombinant VH-D-JH segments translocation belongs to a standard hematooncological investigation. The results are an important prognostic criterion for prediction of expected disease aggressivity and for a minimal residual disease monitoring.
Key words: chronic lymphocytic leukemia, immunoglobulin heavy-chain gene (IgVH), mutation status, somatic hypermutation, prognostic factor.
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