Alteration of p73 in acute myelogenous leukemia.
The frequency of p73 mutation is low in hematologic malignancies as well as solid tumors. In the present study, we scanned for mutations in the exons 4, 5, 6, and 7 of p73, as well as methylation of the CpG island in the untranslated region of exon 1, in 100 de novo AML patients. Four patients showed mutation in exon 5 and one in exon 6, and none of the patients showed mutation in exons 4 and 7. None of the patients showed p73 gene methylation. The expression level of p73 mRNA was also examined in 40 AML samples using reverse transcriptase-polymerase chain reaction. Only six AML patients showed p73 mRNA expression, as analyzed by RT-PCR analysis. However, p73 over-expression in 30% of patients was demonstrated by immunocytochemistry and Western blot analysis. Further, mutation of p73 has been correlated with p73 mRNA and p73 protein status. The results show the presence of over-expressed p73 mRNA and protein in the samples with mutated p73 gene. Thus, it is presumed that mutation of p73 might lead to production of defective p73 protein and p73 mRNA, and this might have a role in the process of leukemogenesis of AML. This report is the first demonstrating the presence of mutations in p73 gene in acute myelogenous leukemia.
Sahu
Geeta Ram
GR
Molecular Oncology and Medical Biotechnology Division, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India. sahugr@yahoo.com
Mishra
Rajakishore
R
Nagpal
Jatin Kumar
JK
Das
Bibhu Ranjan
BR
D000328:Adult; D000368:Aged; D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins