Alteration of p73 in acute myelogenous leukemia

• Published in: American journal of hematology Vol. 79; no. 1; pp. 1 - 7
• Main Authors: GEETA RAM SAHU, MISHRA, Rajakishore, JATIN KUMAR NAGPAL, BIBHU RANJAN DAS
• Format: Journal Article
• Language: English
• Published: New York, NY Wiley-Liss 01.05.2005
• Subjects: Adult; Aged; Base Sequence; Biological and medical sciences; DNA Methylation; DNA Primers; DNA-Binding Proteins - genetics; Exons - genetics; Genes, Tumor Suppressor; Hematologic and hematopoietic diseases; Hematologic Neoplasms - genetics; Humans; Leukemia, Myeloid, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Mutation; Nuclear Proteins - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Tumor Protein p73; Tumor Suppressor Proteins; AML; mutation; Hematology; Acute; methylation; Malignant hemopathy; over-expression; p73; Acute myelocytic leukemia
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20284

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.