PMID- 9432033
OWN - NLM
STAT- MEDLINE
DCOM- 19980123
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 99
IP  - 4
DP  - 1997 Dec
TI  - p53 abnormalities in CLL are associated with excess of prolymphocytes and poor 
      prognosis.
PG  - 848-57
AB  - To determine the role of the p53 gene in chronic lymphocytic leukaemia (CLL) and 
      its possible involvement in the pathogenesis of a progressive form of CLL 
      characterized by > 10%, prolymphocytes (CLL/PL), we selected 32 cases, 17 with 
      typical morphology and 15 CLL/PL. The extent of inactivation of p53 was examined 
      by assessing loss of heterozygosity (LOH) at 17p13.3, by sequencing the highly 
      conserved region (exons 5-9) of the p53 gene and by analysing p53 protein 
      expression. LOH was detected in 8/28 (29%) cases, p53 mutations in 5/32 (16%) 
      cases and p53 expression in 5/27 (19%) cases. Overall 11 cases (30%) had p53 
      abnormalities of which eight cases had CLL/PL. There was a significant 
      association between CLL/PL and p53 abnormalities (P=0.05); 75% of cases with LOH, 
      80% of p53 mutations and 80% of cases positive for p53 protein had CLL/PL. Thus, 
      p53 inactivation is the first gene abnormality identified so far to be involved 
      in the development of CLL/PL. All the cases with typical CLL and p53 
      abnormalities had only one allele affected whereas 4/6 CLL/PL had both alleles 
      inactivated. This difference in the extent of p53 inactivation suggests that 
      accumulation of p53 abnormalities may be associated with progression of CLL to 
      CLL/PL. CLL cases with p53 abnormalities were characterized by a higher incidence 
      of stage C (P<0.025), a higher proliferative rate (P=0.05), short survival 
      (P<0.005) and resistance to first-line therapy (P<0.02) but not to nucleoside 
      analogues. Analysis of the correlation between p53 status and incidence of 
      trisomy 12 by fluorescence in situ hybridization (FISH) showed that trisomy 12 
      was more frequent in cases without p53 abnormalities, suggesting that trisomy 12 
      and p53 may represent different pathways of transformation in CLL.
FAU - Lens, D
AU  - Lens D
AD  - Academic Department of Haematology and Cytogenetics, Institute of Cancer 
      Research, London.
FAU - Dyer, M J
AU  - Dyer MJ
FAU - Garcia-Marco, J M
AU  - Garcia-Marco JM
FAU - De Schouwer, P J
AU  - De Schouwer PJ
FAU - Hamoudi, R A
AU  - Hamoudi RA
FAU - Jones, D
AU  - Jones D
FAU - Farahat, N
AU  - Farahat N
FAU - Matutes, E
AU  - Matutes E
FAU - Catovsky, D
AU  - Catovsky D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
SB  - IM
MH  - Blotting, Southern
MH  - Gene Expression
MH  - Genes, p53/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/pathology
MH  - Leukemia, Prolymphocytic/genetics/pathology
MH  - Loss of Heterozygosity
MH  - Mutation
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Survival Analysis
MH  - Survival Rate
EDAT- 1998/01/31 00:00
MHDA- 1998/01/31 00:01
CRDT- 1998/01/31 00:00
PHST- 1998/01/31 00:00 [pubmed]
PHST- 1998/01/31 00:01 [medline]
PHST- 1998/01/31 00:00 [entrez]
AID - 10.1046/j.1365-2141.1997.4723278.x [doi]
PST - ppublish
SO  - Br J Haematol. 1997 Dec;99(4):848-57. doi: 10.1046/j.1365-2141.1997.4723278.x.