Frequent p53 mutation in relapsed acute lymphoblastic leukemia with cytogenetic instability: a longitudinal analysis.
P53 mutation, through defects in repairing DNA damages, is associated with genomic instability. In 24 adult patients with relapsed acute lymphoblastic leukemia (ALL), the status of the p53 gene at different stages was serially followed by cytogenetic and polymerase-chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis. P53 mutation was detected in 6 patients (25%) and all were at relapsed stages: 3 at first relapse, 2 at second relapse and one at refractory phase. Loss of the remaining p53 allele was demonstrated in 5 of them by cytogenetic and SSCP analysis. Furthermore, all of the p53 mutations were associated with appearance of complex cytogenetic changes (CCG), suggesting of cytogenetic instability (CGI). The frequency of acquiring p53 mutation during leukemic progression is significantly higher in patients with CGI than in patients without CGI (6/11 v 0/13, p = 0.003). P53 mutation was detected either concurrently (n = 2) or after (n = 4, 2(+)-18 months) appearance of CCG. The results suggest that p53 mutation is frequently involved during ALL relapse and is closely linked with cytogenetic instability.
Tang
J L
JL
Department of Internal Medicine, National Taiwan University Hospital, Taipei.
Tien
H F
HF
Lin
M T
MT
Chen
P J
PJ
Chen
Y C
YC
D000328:Adult; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D016158:Genes, p53; D006801:Humans; D007621:Karyotyping; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012008:Recurrence