Genetics of CLL

Chronic lymphocytic leukemia (CLL) of the B-cell type accounts for 30% of all adult leukemia cases, and is therefore the most frequent type of leukemia in adulthood. Specific recurrent chromosome abnormalities are of prognostic value and are associated with specific clinical features in CLL. One aim of our study is the discovery of new characteristic chromosome anomalies by use of several classical and molecular cytogenetic techniques, and to test the prognostic value of these new anomalies. Cytogenetic investigations, including interphase FISH, during the course of the disease will clarify the clinical impact of specific combinations of chromosomal aberrations. In recent models of cancer development the genetic predisposition plays an important role. In contrast to monogenic diseases, which are due to single gene mutations, the genetic background of multifactorial complex diseases, including most types of cancer, has not yet been clarified. An interaction between polymorphic genes and environmental factors is discussed. If this cumulative predisposition crosses a certain threshold, transformation occurs. The genes involved are of low penetrance, and they concern different functional systems, ie. apoptosis, cell cycle regulation and signal transduction. Above all, polymorphisms of genes encoding metabolising and detoxifying enzymes have a special importance for the individual reaction towards carcinogenic and environmental substances. The correlation of cytogenetic data with the results of genotype analyses as well as with clinical features and the course of disease will bring new insights into the mechanisms leading to the emergence of CLL, and could contribute to the development of new therapeutic strategies.

Chronic lymphocytic leukemia (CLL) of the B-cell type accounts for 30% of all adult leukemia cases, and is therefore the most frequent type of leukemia in adulthood. Specific recurrent chromosome abnormalities are of prognostic value and are associated with specific clinical features in CLL. One aim of our study is the discovery of new characteristic chromosome anomalies by use of several classical and molecular cytogenetic techniques, and to test the prognostic value of these new anomalies. Cytogenetic investigations, including interphase FISH, during the course of the disease will clarify the clinical impact of specific combinations of chromosomal aberrations. In recent models of cancer development the genetic predisposition plays an important role. In contrast to monogenic diseases, which are due to single gene mutations, the genetic background of multifactorial complex diseases, including most types of cancer, has not yet been clarified. An interaction between polymorphic genes and environmental factors is discussed. If this cumulative predisposition crosses a certain threshold, transformation occurs. The genes involved are of low penetrance, and they concern different functional systems, ie. apoptosis, cell cycle regulation and signal transduction. Above all, polymorphisms of genes encoding metabolising and detoxifying enzymes have a special importance for the individual reaction towards carcinogenic and environmental substances. The correlation of cytogenetic data with the results of genotype analyses as well as with clinical features and the course of disease will bring new insights into the mechanisms leading to the emergence of CLL, and could contribute to the development of new therapeutic strategies.