[Molecular genetic characterization of chronic lymphocytic leukemia aggressivity in Czech patients: a nucleotide variability of genes coding for heavy chain of immunoglobulin].
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 J, subgenes in malignant population of B-cells.


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 V I 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-J11 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.
Kuhrová
V
V
Centrum molekulární biologie a genové terapie FN, Brno. vkuhrova@fnbrno.cz
Francová
H
H
Klimesová
D
D
Brychtová
Y
Y
Doubek
M
M
Trbusek
M
M
Brejcha
M
M
Dvoráková
D
D
Mayer
J
J
D001483:Base Sequence; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D014178:Translocation, Genetic
D007135:Immunoglobulin Variable Region