PMID- 11486330
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20191105
IS  - 1127-0020 (Print)
IS  - 1127-0020 (Linking)
VI  - 4
IP  - 1
DP  - 2000 Mar
TI  - Genetic features of B-cell chronic lymphocytic leukemia.
PG  - 48-72
AB  - The genetic features of B-cell chronic lymphocytic leukemia (CLL) are currently 
      being reassessed by molecular cytogenetic techniques such as fluorescence in situ 
      hybridization (FISH). Conventional cytogenetic studies by chromosome banding are 
      difficult in CLL mainly because of the low in vitro mitotic activity of the tumor 
      cells, which leads to poor quantity and quality of metaphase spreads. Molecular 
      genetic analyses are limited because candidate genes are known for only a few 
      chromosomal aberrations that are observed in CLL. FISH was found to be a powerful 
      tool for the genetic analysis of CLL as it overcomes both the low mitotic 
      activity of the CLL cells and the lack of suitable candidate genes for analysis. 
      Using FISH, the detection of chromosomal aberrations can be performed at the 
      single cell level in both dividing and non-dividing cells, thus circumventing the 
      need of metaphase preparations from tumor cells. Probes for the detection of 
      trisomies, deletions and translocation breakpoints can be applied to the regions 
      of interest with the growing number of clones available from genome-wide 
      libraries. Using the interphase cytogenetic FISH approach with a disease specific 
      set of probes, chromosome aberrations can be found in more than 80% of CLL cases. 
      The most frequently observed abnormalities are losses of chromosomal material, 
      with deletions in band 13q14 being the most common, followed by deletions in 
      11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of 
      chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in 
      particular involving the immunoglobulin heavy chain locus at 14q32, which are 
      frequently observed in other types of non-Hodgkin's lymphoma, are rare events in 
      CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in 
      cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated 
      in a subset of cases with 11q22-q23 aberrations. However, for the other 
      frequently affected genomic regions, the search for candidate genes is ongoing. 
      In parallel, the accurate evaluation of the incidence of chromosome aberrations 
      in CLL by FISH allows the correlation of genetic abnormalities with clinical 
      disease manifestations and outcome. In particular, 17p abnormalities and 
      deletions in 11q22-q23 have already been shown to be among the most important 
      independent prognostic factors identifying subgroups of patients with rapid 
      disease progression and short survival. In addition, deletion 17p has been 
      associated with resistance to treatment with purine analogs. Therefore, genetic 
      abnormalities may allow a risk assessment for individual patients at the time of 
      diagnosis, thus giving the opportunity for a risk-adapted management.
FAU - Stilgenbauer, S
AU  - Stilgenbauer S
AD  - Department of Internal Medicine III, University of Ulm, Germany.
FAU - Lichter, P
AU  - Lichter P
FAU - Dohner, H
AU  - Dohner H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Italy
TA  - Rev Clin Exp Hematol
JT  - Reviews in clinical and experimental hematology
JID - 9815344
SB  - IM
MH  - Chromosome Aberrations/genetics
MH  - *Cytogenetic Analysis
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics
RF  - 138
EDAT- 2001/08/07 10:00
MHDA- 2001/10/05 10:01
CRDT- 2001/08/07 10:00
PHST- 2001/08/07 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/08/07 10:00 [entrez]
AID - 10.1046/j.1468-0734.2000.00003.x [doi]
PST - ppublish
SO  - Rev Clin Exp Hematol. 2000 Mar;4(1):48-72. doi: 10.1046/j.1468-0734.2000.00003.x.