Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the structural alteration of the p53 gene, by Southern blotting with conventional and/or pulsed-field gel electrophoresis, in patients with Philadelphia chromosome-positive leukemia (chronic myelogenous leukemia; CML, 34 cases and acute leukemia; AL, 5 cases). We found an alteration of the p53 gene in one of 5 AL patients. Loss of heterozygosity was detected in two CML patients with i(17q) chromosome, but we could find no other alterations in the remaining CML patients.
 ...
PMID:Alterations of the p53 gene in Philadelphia chromosome-positive leukemia including chronic myelogenous leukemia and acute leukemia. 139 1

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
 ...
PMID:[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. 163 23

We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.
 ...
PMID:[Rearrangement and expression of bcr-abl genes in CML and ALL]. 189 Jul 38

A new Ph1-positive leukemic cell line (MC3) expressing the P210bcr/abl oncoprotein was established from a patient with CML in blast crisis. The MC3 cells showed the trilineage phenotype of myeloid, lymphoid (CD19) and megakaryocytoid lineages, and had a proliferative response to rhIL-1 and rhIL-3 in the serum-free culture. These results and the expression of CD34 indicated that the MC3 cells have characteristics of hematopoietic progenitor cells. Recently, it has been documented that alterations of the p53 gene in leukemic cells are frequently detected during the blast crisis of CML. The MC3 cells contained the altered p53 gene. In addition, the original leukemic cells showed the point-mutational activation of the N-ras gene and an additional chromosomal abnormality inv(3q), but the MC3 cells contained no such abnormalities, indicating that not all of the original leukemic cells had these abnormalities. Thus, the MC3 cell line may provide several insights into investigations of the blast crisis in CML as well as hematopoietic progenitor cells.
 ...
PMID:Establishment and characterization of a new Ph1-positive chronic myeloid leukemia cell line MC3 with trilineage phenotype and an altered p53 gene. 778 56

We looked for MDM2 gene amplification and over-expression by Southern and Northern blot analysis in 135 and 66 cases of haematological malignancies, including ALL, AML, CML in chronic phase, CLL, MDS, PLL, non-Hodgkin's lymphoma (NHL) and myeloma. No amplification of the gene was found. An over-expression of MDM2 RNA was seen in 9/66 (14%) patients tested, including 3/9 ALL, 3/24 AML, 2/4 myelomas, 1/1 PLL, but 0/2 CML, 0/2 NHL and 0/21 MDS. None of the patients over-expressing MDM2 had modifications of P53 gene transcript or p53 mutations. Most of the patients over-expressing MDM2 gene had poor prognostic features (including 'unfavourable' cytogenetic abnormalities), poor response to chemotherapy and short survival. Our findings suggest that over-expression of MDM2 is seen in a relatively small number of haematological malignancies, and is associated with poor prognosis.
 ...
PMID:Over-expression of the MDM2 gene is found in some cases of haematological malignancies. 780 95

A patient with typical Ph1-positive CML was studied during sequential phases: (1) initial chronic phase, (2) first myeloid blast crisis, (3) second chronic phase, and (4) accelerated disease leading to a second blast crisis. A point mutation in codon 239 of the p53 gene and a novel chromosome 17 alteration appeared concomitantly with the first blast crisis and then disappeared with re-establishment of a second chronic phase. They did not reappear with the second acute phase, indicating that the clone responsible for the original blast crisis had been suppressed and supplanted by another clone of malignant cells. This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone, but that the underlying molecular defect in haemopoietic cells (in this case the c-ABL translocation) persists and other aggressive clones with different molecular lesions eventually arise. Our observations and inferences are consistent with the hypothesis advanced by Fialkow et al (1991) to explain clonal remissions in acute non-lymphocytic leukaemia.
 ...
PMID:Sequential relapses of blastic crisis may involve different clones of cells with different molecular abnormalities. 799 8

Parts of the Bcr/Abl hybrid transcript supposed to be important for its transforming ability were sequenced in a series of CML blast crises, in order to evaluate the possible presence of alterations responsible for the disease transition from the chronic to the acute phase. In addition, the N- and Ki-ras as well as the p53 involvement was investigated by exploring their structure and expression in the same patients. We used traditional types of molecular analysis including Southern and Northern blot, together with methods that allow a rapid detection of point mutations and microdeletions, such as SSCP, single strand conformation polymorphism and direct sequencing. The results obtained may be summarized as follows: no alterations were found in the parts of the Bcr/Abl transcripts investigated in the present study (SH2, SH3 and the region surrounding codon 832); p53 alterations were observed in 5% and N- and Ki-RAS mutations in 5% of the cases examined. These molecular defects are therefore responsible for the clinical progression of the Ph1-positive CML only in a minority of cases.
 ...
PMID:Molecular defects associated with the acute phase CML. 825 5

The retinoblastoma susceptibility gene (RB) and p53 gene are now known to be the prototypes for a class of tumor suppressor genes. Both genes act as a regulator of cell cycle transition at G1/S in many types of cell lineages. Underphosphorylated form of RB protein (Rd) acts as a growth suppressor by blocking exit from G1 through a specific binding to E2F or promoter region of certain growth-associated genes. Phosphorylation of Rb can be viewed as inactivating Rb and allowing cell cycle progression to occur. Differentiation of hematopoietic cell is accompanied with the loss of ability to phosphorylate Rb, indicating that Rb plays an important role in hematopoietic cell growth and differentiation. Abnormalities of RB gene may, therefore, predispose to the development of hematologic malignancies. DNA rearrangement was reported to be present in 1.5-12.1% of cases with primary leukemias, and the absence of RB protein was also observed in 6.3-23.2%. The abnormalities of p53 gene were also frequently observed in hematologic malignancies. DNA rearrangement of p53 was observed in 20-30% of the cases with blastic crisis of CML. Point mutation at the "hot spot" was reported in many types of leukemias, especially in cell lines established from these cases.
 ...
PMID:[Tumor suppressor genes and their role in abnormal production of leukocytes (leukemogenesis)]. 831 27

Molecular events associated with the transformation into blast crisis phase in Ph1-positive CML were analyzed in the present study. The 9;22 chromosomal translocation in CML generates the bcr/abl fused gene coding P210bcr/abl that has enhanced tyrosine kinase activity. In 55 CML cases, Southern and RT-PCR analysis revealed that breakpoints of the bcr gene on chromosome 22q11 were clustered in M-bcr, except for one case and no obvious difference was observed between chronic and crisis phases. However, blast crisis cells displayed enhanced the expression of bcr/abl mRNA, when compared with those in chronic phase cells. By DNA transfection and PCR analysis, the point-mutational activation of N-ras oncogene was rarely identified, and no point-mutational activation of fms gene was found in the crisis phase cases. On the other hand, 2 out of 13 crisis cases contained gross alteration of p53 anti-oncogene. Furthermore, all 4 myeloid crisis cases and K562 cells showed disappearance of the P53 transcript, and MC3 cells derived from a myeloid crisis case showed an aberrant transcript, whereas chronic phase cases, Ph1-positive ALL cell lines and lymphoid crisis cases including NALM-1 cells showed normal expression of the P53 gene. At present, the precise mechanism associated with the blastic trans-formation in CML remain to be determined. The present study suggested one possibility that a selective and progressive process of Ph1 clone with high expression of the bcr/abl gene may be involved with the transformation into non-lymphoid crisis phases from chronic phases. In addition, this progression may be accelerated by the alteration of p53 anti-oncogene, or/and rarely by the point-mutational activation of ras oncogene family.
 ...
PMID:[Molecular analysis of transformation into blast crisis in chronic myelogenous leukemia]. 850 66

p21 is induced by and mediates the effects of p53 in response to DNA damage arresting the cell in G1 or G2, by inhibiting multiple cyclin-cyclin-dependent kinases (CDK) or binding to proliferating-cell nuclear antigen (PCNA), respectively. To determine whether p21 mutants occur in tumors we examined DNA from 188 primary non-Hodgkin's B-cell lymphoma (NHL) tumors and 84 chronic myelogenous leukemia samples for mutational changes in the coding region of p21 by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA. We did not find mutations in the coding region in these two tumor types. We identified a polymorphic nucleotide change in codon 31 in which a transversion from C to A substituted amino acid arginine for serine. Three of 188 NHL tumors were homozygous for this change, but they were not identified in 84 CMLs or in 97 normal controls. On the other hand, in one CML case a transition from G to A in codon 64 substituted amino acid threonine for alanine. These data do not indicate that derangements in the coding region of p21 contribute to the initiation and/or progression of these tumors.
 ...
PMID:Absence of somatic changes in p21 gene in non-Hodgkin's lymphoma and chronic myelogenous leukemia. 865 61


1 2 3 4 Next >>