¹Abteilung Innere Medizin III, University of Ulm, Germany

²Abteilung 'Organisation komplexer Genome', Deutsches Krebsforschungszentrum, Heidelberg, Germany

Correspondence to: H Döhner, Department of Internal Medicine III, University of Ulm, Robert-Koch-Str 8, 89081 Ulm, Germany; Fax: 49 731 500 24493

The genetic characterization of chronic lymphocytic leukemia (CLL) has made significant progress over the past few years. While conventional cytogenetic analyses only detected chromosome aberrations in 40-50% of cases, new molecular cytogenetic methods, such as fluorescence in situ hybridization (FISH), have greatly enhanced our ability to detect chromosomal abnormalities in CLL. Today, genomic aberrations are detected in over 80% of CLL cases. Genes potentially involved in the pathogenesis were identified with ATMin a subset of cases with 11q deletion and p53 in cases with 17p13 deletion. For the most frequent aberration, the deletion 13q14, candidate genes have been isolated. Genetic subgroups with distinct clinical features have been identified. 11q deletion is associated with marked lymphadenopathy and rapid disease progression. 17p deletion predicts for treatment failure with alkylating agents, as well as fludarabine and short survival times. In multivariate analysis 11q and 17p deletions provided independent prognostic information. Recently, another important issue of genetic risk classification in CLL was identified with the mutation status of the immunoglobulin variable heavy chain genes (V_H). CLL cases with unmutated V_H show more rapid disease progression and shorter survival times. Whether CD38 expression can serve as a surrogate marker for V_H mutation status is currently discussed controversially. V_H mutation status and genomic abnormalities, such as 17p and 11q deletion, have recently been shown to be related to each other, but were of independent prognostic information in multivariate analysis. Moreover, genomic aberrations and V_H mutation status appear to give prognostic information irrespective of the clinical stage and may therefore allow a risk assessment for individual patients early in the course of their disease.

Leukemia (2002) 16, 993-1007. DOI: 10.1038/sj/leu/2402537

CLL; genomic aberrations; p53; ATM; V_Hmutation status