p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia.
Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic, and smoldering. We studied the relationship between p53 gene alteration and clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and five crisis type transformed from chronic type. Using a polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by nucleotide sequencing, we detected mutations of the p53 gene in six of the 14 acute type patients, two of the five crisis type, and one of the 15 chronic type patients. Gene dosage studies, using PCR amplification and Southern blotting, showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type patients, two of the five crisis type, and one of 14 chronic type patients examined. These observations indicated that the frequency of p53 gene alterations in the acute and crisis types of ATL was markedly higher than that in chronic type, suggesting that p53 gene alteration plays a role in the disease progression of ATL.
Nishimura
S
S
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Asou
N
N
Suzushima
H
H
Okubo
T
T
Fujimoto
T
T
Osato
M
M
Yamasaki
H
H
Lisha
L
L
Takatsuki
K
K
D000328:Adult; D000368:Aged; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D016368:Frameshift Mutation; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D017931:DNA Primers; D016159:Tumor Suppressor Protein p53