PMID- 22509718
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20220419
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 89
IP  - 1
DP  - 2012 Jul
TI  - High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center 
      interphase fluorescence in situ hybridization study and review of the literature.
PG  - 72-80
LID - 10.1111/j.1600-0609.2012.01790.x [doi]
AB  - BACKGROUND: We studied the relation of clonal evolution (CE) in Chronic 
      B-lymphocytic leukemia (CLL) with prognostic factors and the correlation between 
      CE and disease progression and overall survival. METHODS: With interphase 
      fluorescence in situ hybridization (FISH) analysis, we looked for 11q22 deletion, 
      17p13 deletion, and trisomy 12. A second FISH was performed approximately 3 yr 
      after the first one or earlier in case of disease progression. RESULTS: High-risk 
      CE, defined as the acquisition of a new 11q or 17p deletion, was observed in 
      11.5% (11/95) of patients with CLL. The relative risk of CE was not influenced by 
      CD38 and ZAP-70 expression, mutational status of the immunoglobulin heavy chain 
      gene (IgVH), lymphocyte doubling time, and genomic aberrations observed with the 
      first FISH or by treatment given between the sequential genetic analyses. 
      Patients with high-risk CE had a significant shorter survival time (59 months vs. 
      not reached, P = 0.0367). Multivariate analysis identified CE as the strongest 
      independent prognostic marker regarding survival [hazard ratio (HR) 4.1, P = 
      0.01]. Clonal fluctuation, defined as disappearance of the 11q or 17p deletion, 
      was seen in 11.5% (11/95) of patients. Most patients lost the high-risk clone 
      after treatment despite persistence of a malignant clone. The disappearance of 
      these genomic aberrations did not ameliorate outcome. A few patients have lost 
      spontaneously a small 17p clone. CONCLUSION: This study confirms that CE and 
      clonal fluctuation are common phenomena in CLL. CE was not limited to patients 
      with pre-existing adverse prognostic factors. Acquiring high-risk CE was 
      identified as the strongest independent prognostic factor for impaired survival.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Janssens, Ann
AU  - Janssens A
AD  - Department of Haematology, Ghent University Hospital, Ghent, Belgium. 
      Ann.janssens@uz.kuleuven.be
FAU - Van Roy, Nadine
AU  - Van Roy N
FAU - Poppe, Bruce
AU  - Poppe B
FAU - Noens, Lucien
AU  - Noens L
FAU - Philippe, Jan
AU  - Philippe J
FAU - Speleman, Frank
AU  - Speleman F
FAU - Offner, Fritz
AU  - Offner F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120507
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin Variable Region)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase 1/genetics
MH  - Adult
MH  - Aged
MH  - Chromosome Aberrations
MH  - *Clonal Evolution
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression
MH  - Humans
MH  - Immunoglobulin Heavy Chains/genetics
MH  - Immunoglobulin Variable Region/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/mortality/therapy
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Prognosis
MH  - Review Literature as Topic
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - ZAP-70 Protein-Tyrosine Kinase/genetics
EDAT- 2012/04/19 06:00
MHDA- 2012/09/11 06:00
CRDT- 2012/04/19 06:00
PHST- 2012/04/08 00:00 [accepted]
PHST- 2012/04/19 06:00 [entrez]
PHST- 2012/04/19 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
AID - 10.1111/j.1600-0609.2012.01790.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2012 Jul;89(1):72-80. doi: 10.1111/j.1600-0609.2012.01790.x. Epub 
      2012 May 7.