Analysis of p53 gene mutations in acute myeloid leukemia.
We have previously reported the absence of mutations within exons 5-9 of the p53 gene in a panel of 30 cases of acute promyelocytic leukemia (APL), which represent the M3 FAB type of acute myeloid leukemia (AML). In the present report, we extend our analysis of p53 gene mutations to 70 cases of AML representative of the other FAB types of the disease, including M1 (16 cases), M2 (20 cases), M4 (17 cases), M5 (12 cases), and M6 (5 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified products. Mutant p53 alleles were detected in 5 of 70 cases; 1 case in exon 5, 2 cases in exon 6, and 2 cases in exon 7. The alterations of the p53 gene were represented by point mutation leading to an amino acid substitution in four cases, and deletion in the remaining case. In four of the five cases, direct sequencing indicated the loss of the normal p53 allele; in the remaining case, two mutations were detected, presumably involving both p53 alleles. Three cases showed mutations at diagnosis; in the remaining two, the mutations were observed in clinical relapse but not at diagnosis. Our results confirm the relatively low incidence of p53 mutations in AML and further support the evidence that p53 plays a role in leukemogenesis through a recessive mechanism (two-hit model) of inactivation of tumor suppressor activity.
Trecca
D
D
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Università di Milano, Ospedale Maggiore, Italy.
Longo
L
L
Biondi
A
A
Cro
L
L
Calori
R
R
Grignani
F
F
Maiolo
A T
AT
Pelicci
P G
PG
Neri
A
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004277:DNA, Single-Stranded / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004277:DNA, Single-Stranded; D016159:Tumor Suppressor Protein p53