CHANGING P53 MUTATIONS WITH THE EVOLUTION OF CHRONIC MYELOID-LEUKEMIA FROM THE CHRONIC PHASE TO BLAST CRISIS

被引:19
|
作者
GUINN, BA [1 ]
SMITH, M [1 ]
PADUA, RA [1 ]
BURNETT, A [1 ]
MILLS, K [1 ]
机构
[1] UNIV WALES COLL MED,DEPT HAEMATOL,LRF PRELEUKAEMIA UNIT,CARDIFF CF4 4XN,S GLAM,WALES
关键词
P53; MUTATIONS; CLONAL EVOLUTION; CML DISEASE PROGRESSION;
D O I
10.1016/0145-2126(95)00024-I
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The frequent involvement of chromosome 17p abnormalities in the progression of chronic myeloid leukaemia (CML) led us to investigate the involvement of the p53 tumour suppressor gene located on chromosome 17p. We analysed 31 samples from four patients sequentially, and 16 patients in blast crisis only, using single stranded conformational polymorphism (SSCP) analysis of exons 5-8, followed by cloning and sequencing. The sequential samples ranged from diagnosis through to late disease. We found that 15% of our blast crisis samples had p53 abnormalities, In our sequential studies we found two of the four patients analysed in more detail had p53 mutations in the late chronic phase of disease (11 and 5 months prior to blast crisis becoming apparent). These chronic phase mutations differed from the p53 abnormalities found in the blast crisis samples from these patients. One patient: also had the same chronic phase mutation at post bone marrow transplant relapse. Our results suggest that, in some cases, sequential investigations through CML disease progression of p53 mutations and other oncogenes/proto-oncogenes may provide early indications of the routes of disease progression to blast crisis.
引用
收藏
页码:519 / 525
页数:7
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