The P53 gene has the important functions including induction of apoptosis, regulation of cell cycle, repair of DNA damage. The mutation of the P53 gene exists in more than 50% of human tumors and 13% of hematological malignancies. The P53 gene abnormality is closely related with the clinical course and prognosis of leukemia. The P73 or P63 gene, the member of the P53 family not only possesses similar to P53 activity of inducing apoptosis, activating transcription, but also plays different biological effects according to protein structural diversity, and even antagonises the function of the P53 gene. Researchers found that P73 or P63 gene also has the dual characteristics of the tumor suppressor and oncogene, and shows different expression and function in different types, different stages of leukemia. In this article, P53 family (P53, P73, P63) gene structure, biological function and the relationship of the three genes with the course, prognostic outcome, treatment and other clinical features of the leukemia are reviewed.
Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Leukemia ; diagnosis ; genetics ; pathology ; Tumor Suppressor Protein p53 ; genetics

Adult ; Cytogenetics ; Genes, p53 ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/genetics*

OBJECTIVES: Mutation of p53 may play a role in manifestation of rheumatoid arthritis synovium, but several studies on p53 expression in synovial tissues of rheumatoid arthritis showed conflicting results. We investigated the amount and pattern of p53 positive cells in rheumatoid arthritis synovium, in comparison with osteoarthritis synovium, by using immunohistochemistry with two other monoclonal antibodies for p53. METHODS: Synovial tissues from 9 patients with rheumatoid arthritis and 5 patients with osteoarthritis were examined for p53 expression by immunohistochemistry with 2 monoclonal antibodies for p53, DO-1 and DO-7. Histologic features of inflammation were also scored and compared with p53 expression. RESULTS: There was no significant difference between inflammatory scores in both groups. In the synovial tissues of rheumatoid arthritis patients, p53 positive cells were detected in 3 out of 9 samples(33%) and p53 expressions were restricted to inflammatory mononuclear cells, but synovial lining cells, subsynovial fibroblast-like cells and vascular endothelial cells were p53 negative. p53 expressions in osteoarthritis synovial tissues as control were observed in 2 out of 5 samples(40%) and the amount and pattern of p53 positive cells were comparable to those seen in rheumatoid arthritis synovial tissues. There was no demonstrable correlation between the synovial tissues of both groups with respect to inflammation scores and expression of p53 protein. CONCLUSION: Our findings suggest that altered p53 expression may not play a significant role in the manifestation of rheumatoid arthritis synovium. However these data need to be strengthened by increasing the number of samples and molecular biology approaches.
Arthritis, Rheumatoid/metabolism* ; Arthritis, Rheumatoid/genetics ; Comparative Study ; Gene Expression ; Genes, p53 ; Human ; Immunohistochemistry ; Osteoarthritis/metabolism ; Osteoarthritis/genetics ; Protein p53/metabolism* ; Protein p53/genetics ; Synovial Membrane/metabolism

Adenoviridae ; genetics ; Genes, p53 ; Genetic Therapy ; methods ; Genetic Vectors ; Humans ; Neoplasms ; therapy ; RNA Interference ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo observe the effect of recombinant adenovirus-mediated wild-type p53 gene on the number and proteins of centrosome in K562 cells. To explore the possibility of application of wild-type p53 gene therapy in the treatment of chronic myeloid leukemia.

METHODSThe recombinant adenoviruses carrying wild-type p53 gene (Ad5 wtp53), mutant p53 gene (Ad5 mtp53) or the green fluorescent protein (GFP) gene was repeatedly amplified and co-infected into K562 cells with cation polybrene. The optimal infection titer and infection time of the recombinant adenoviruses were determined by MTT assay, p53 mRNA and protein expression were determined by RT-PCR and Western blot respectively. The centrosomal structural protein gamma-tubulin and the spindle protein alpha-tubulin were marked simultaneously by indirect immunofluorescence staining, and the expression of the centrosomal gamma-tubulin protein, the mitosis and the number of centrosome were observed under the laser confocal microscopy.

RESULTSInfection efficiency with recombinant adenoviruses was facilitated by polybrene in K562 cells, and 4 microg/ml polybrene was chosen. The optimal adenovirus infection titer was 20,000 MOI and the optimal infection time was 72 hours. p53 mRNA and P53 protein can be expressed in K562 cells by Ad5wtp53 and Ad5mtp53. Both the expression of the centrosomal gamma-tubulin protein and the number of centrosomes were decreased after Ad5wtp53 infection.

CONCLUSIONThere is sustained expression of P53 protein in K562 cells after its infection by Ad5wtp53. Wild-type P53 protein can lead to the down-regulation of the number of centrosomes and the expression of centrosomal gamma-tubulin protein in K562 cells.

Adenoviridae ; genetics ; Centrosome ; metabolism ; Genes, p53 ; genetics ; Genetic Vectors ; Humans ; K562 Cells ; Transfection ; Tubulin ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Genes, p53 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/genetics* ; Tumor Suppressor Protein p53/genetics*

p53 is considered as the "master regulator" in DNA damage-induced cell apoptosis. However, p53 is the most frequently mutated gene in human cancers (more than 50 %). Thus the research of p53-independent pathway in cell apoptosis may ultimately provide new therapeutic opportunities for many cancers. It has been shown that Caspase 2, p73, p63, and NF-kappa B-related signaling pathways are involved in DNA damage-induced, p53-independent cell apoptosis. This article reviews the recent research progress in these signaling pathways.
Apoptosis ; genetics ; DNA Damage ; Humans ; Signal Transduction ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVE: To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R). METHODS: Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared. RESULTS: Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05). CONCLUSION Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.
DNA Mutational Analysis ; Humans ; Incidence ; Mutation ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Tumor Suppressor Protein p53 ; genetics

Adenoviridae/genetics* ; Consensus ; Head and Neck Neoplasms/therapy* ; Humans ; Tumor Suppressor Protein p53/genetics*

To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.
Carcinoma/genetics/pathology ; Exons ; *Genes, p53 ; Humans ; Metaplasia/genetics/pathology ; *Microsatellite Repeats ; *Mutation ; Precancerous Conditions ; Stomach/*pathology ; Stomach Neoplasms/genetics/pathology ; Tumor Suppressor Protein p53/genetics/metabolism