p73 mutations and expression in adult de novo acute myelogenous leukemia.
The p73 gene is a candidate tumor suppressor gene that has significant homology to p53. Thus far, p73 has not been investigated in hematopoietic malignancies. We used single-strand conformation polymorphism analysis to examine 60 de novo acute myelogenous leukemia (AML) patients for p73 mutations in exons 4, 6 and 7, which are homologous to the most frequently mutated exons in p53. Mutations were not found, but we did identify polymorphisms in exons 4 and 7. We also examined p73 RNA expression in 15 AML samples, eight cell lines, and eight normal bone marrows using the reverse transcriptase/polymerase chain reaction assay. All 31 RNA samples had p73 expression. Fourteen RNA samples were informative for allelic expression, being heterozygous for a polymorphism in codon 173 of exon 4. The two normal bone marrows and the K562 cell line had evidence of biallelic expression while six of 10 AML patients and the Kasumi (AML) cell line had monoallelic expression. These data suggest that functional p73 mutations in exons 4, 6 and 7 do not occur in most de novo AML patients. In addition, biallelic expression of p73 occurs in normal bone marrows, some AML samples, and specific cell lines. Lastly, monoallelic p73 expression appears to be common in de novo AML.
Stirewalt
D L
DL
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98109, USA.
Clurman
B
B
Appelbaum
F R
FR
Willman
C L
CL
Radich
J P
JP
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000483:Alleles; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins