Molecular Genetic Characterization of Chronic Lymphocytic Leukemia
Aggressivity in Czech Patients: A Nucleotide Variability of Genes Coding for Heavy Chain of Immunoglobulin
1Kuhrová V., 1Francová H., 1Klimešová D. , 2Brychtová Y., 2Doubek M., 1Trbušek M., 3Brejcha M., 1Dvořáková D., 1,2Mayer J.
1Centrum molekulární biologie a genové terapie FN, Brno 2Interní hematoonkologická klinika FN, Brno 3PaR LAB s.r.o., onkohematologická ambulance, Nový Jičín
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.
chronic lymphocytic leukemia, immunoglobulin heavy-chain gene (IgVH), mutation status, somatic
hypermutation, prognostic factor.