Chronic lymphocytic leukemia: mutationalstatus of the immunoglobulin heavy chain gene is a significant prognostic marker

Overview

B-cell chronic lymphocytic leukemia (B-CLL) is the most frequent adult type of leukemia in theWesterncountries. It is characterized by the therapeutically uncontrolled accumulation of functionally incompetentlymphocytes in bone marrow, blood and lymph nodes. The development of the disease isheterogenous with distinctive clinical features and individual evaluation of aggresivity is highlyrecommended for optimal treatment. For this purpose FISH method of identification of genomicaberrations could be used. At present, the new prognostic criterion is accepted – determination of themutational status of variable region VH of the immunoglobulin heavy chain. This aspect, comparingtumor B-cell nucleotide sequence homology with a germline, separates CLL into two different subsetswith markedly different prognoses. A group with an unmutated VH genes with sequence homology >98% displays progressive disease in contrast to the second group with mutated VH genes and homology< 98%, which represents slowly progressive disease. In the last few years PCR method has beendeveloped for detection of malignant clonal specific expansion and for VDJ rearrangement. Usingspecific primers it is possible to amplify, sequence and detect the mutations in VH region. Therelationship of the VH mutation status to the genomic aberrations and differential influence of thesefactors on the pathogenesis and progression of B-CLL are the subject of intensive research. Correlationof mutation status with telomere length and cytosine methylation level has been also observed.

Key words:
chronic lymphocytic leukemia, immunoglobulin heavy chain gene, VDJ subgene rearrangement,VH mutational status, prognostic criterium of the aggresivity CLL