Analysis of the p53 gene in patients with isochromosome 17q and Ph1-positive or -negative myeloid leukemia.
Increased incidence of p53 gene aberrations or chromosome 17p monosomy resulting from an isochromosome 17q [i(17q)] has been observed with transition of chronic myelogenous leukemia (CML) to myeloid blast crisis (BC), and in some patients with poor risk acute myeloid leukemia (AML) progressing from myelodysplastic syndrome (MDS). These data suggested that disease progression may be linked to bi-allelic inactivation of p53. Here, we report on p53 gene analyses of nine patients with CML-BC and AML who showed an i(17q) as characteristic cytogenetic anomaly. Using Southern blots, agarose gel electrophoresis and single-strand conformation polymorphism analyses of PCR products from genomic DNA and cDNA, spanning exons 4 through 9, we did not detect any structural abnormalities of the remaining p53 allele. These findings question the hypothesis that p53 gene alterations are the principal molecular event responsible for progression of CML chronic phase or MDS to i(17q)-positive CML-BC or AML, respectively.
Department of Internal Medicine, West German Cancer Center Essen, University of Essen Medical School.
J
J
Schütte
B
B
Opalka
R
R
Becher
W
W
Bardenheuer
S
S
Szymanski
A
A
Lux
S
S
Seeber
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides