Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia.
The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease.
Peller
S
S
Department of Hematology Assaf-Harofe Medical Center, Zerifin, Israel.
Yona
R
R
Kopilova
Y
Y
Prokocimer
M
M
Goldfinger
N
N
Uysal
A
A
Karabulut
H G
HG
Tukun
A
A
Bokesoy
I
I
Tuncman
G
G
Rotter
V
V
D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007438:Introns; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation
D004273:DNA, Neoplasm