PMID- 12040431
OWN - NLM
STAT- MEDLINE
DCOM- 20020624
LR  - 20130304
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 16
IP  - 6
DP  - 2002 Jun
TI  - Genetics of chronic lymphocytic leukemia: genomic aberrations and V(H) gene 
      mutation status in pathogenesis and clinical course.
PG  - 993-1007
AB  - 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 ATM in 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.
FAU - Stilgenbauer, S
AU  - Stilgenbauer S
AD  - Abteilung Innere Medizin III, University of Ulm, Germany.
FAU - Bullinger, L
AU  - Bullinger L
FAU - Lichter, P
AU  - Lichter P
FAU - Dohner, H
AU  - Dohner H
CN  - German CLL Study Group (GCLLSG). Chronic lymphocytic leukemia
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin Variable Region)
SB  - IM
MH  - *Chromosome Aberrations
MH  - Cytogenetic Analysis
MH  - Disease Progression
MH  - *Genes, Immunoglobulin
MH  - Genome, Human
MH  - Humans
MH  - Immunoglobulin Heavy Chains/genetics
MH  - Immunoglobulin Variable Region/genetics
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics/mortality
MH  - Mutation
MH  - Survival Rate
RF  - 186
EDAT- 2002/06/01 10:00
MHDA- 2002/06/25 10:01
CRDT- 2002/06/01 10:00
PHST- 2002/02/15 00:00 [received]
PHST- 2002/02/22 00:00 [accepted]
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/06/25 10:01 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - 10.1038/sj.leu.2402537 [doi]
PST - ppublish
SO  - Leukemia. 2002 Jun;16(6):993-1007. doi: 10.1038/sj.leu.2402537.