IgVH Gene in CLL Analyzed in the Czech Republic

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Cas Lek Cesk. 2006;145(11):855-8; discussion 859-60. Links

[Molecular genetic characterization of chronic lymphocytic leukemia

aggressivity in Czech patients: a nucleotide variability of genes

coding for heavy chain of immunoglobulin][Article in Czech]

Kuhrova V, Francova H, Klimesova D, Brychtova Y, Doubek M, Trbusek

M, Brejcha M, Dvorakova D, Mayer J.

Centrum molekularni biologie a genove terapie FN, Brno.

vkuhrova@...

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.

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 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.

PMID: 17168419 [PubMed - in process]