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

Specimens from 23 patients with enteropathy-associated T cell lymphoma were studied by immunohistochemistry after antigen retrieval. Specimens from 14 of these patients were investigated for the presence of clonal T cell gene rearrangements in both the tumor and the adjacent enteropathic intestine by the polymerase chain reaction. Primers for T cell receptor beta and gamma genes were used in a combination that permits the identification of approximately 90% of T cell receptor rearrangements. Clonal rearrangements of the T cell receptor were found in 13 of the 14 tumors studied. Specimens of enteropathic bowel resected with the tumor, but showing no morphological or immunohistochemical evidence of tumor involvement, showed clonal T cell receptor gene rearrangements in 11 cases. In 10 of these, the amplified DNA was of the same molecular weight in the enteropathic bowel as in the corresponding tumor. In 2 cases, sequencing the polymerase chain reaction product showed identical T cell receptor gene rearrangements in the tumor and in the adjacent intestine. Uniform staining for p53 was seen in 22 of the 23 tumors. In 9 of 19 cases studied, collections of small lymphocytes in the enteropathic bowel expressed p53. In all but one of these specimens, a clonal rearrangement of the T cell receptor genes was identified. We interpret these findings as support for the concept that enteropathy-associated T cell lymphoma arises on a background of gluten-sensitive enteropathy with evolution of neoplastic T cell clones from the reactive T cell population present in the enteropathic bowel.
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PMID:Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma. 785 60

The induction of apoptosis following topoisomerase inhibitors proceeds in at least three distinct steps: (1) induction of cleavable complexes (potentially lethal damage), (2) topoisomerase-induced DNA damage, and (3) a presently unknown sequence of events that must either lead to cell cycle arrest (G2-block, differentiation) or apoptosis. DNA degradation provides a convenient way to quantify apoptosis in HL-60 cells. Extensive apoptosis can be induced rapidly in undifferentiated HL-60 cells without prevention by cycloheximide or actinomycin D. Therefore, HL-60 cells appear to express constitutively the apoptotic machinery that may be kept under control of a yet unknown repressor. The absence of the tumor suppressor p53 and the presence of bcl-2 are in contrast with the sensitivity of these cells to apoptosis. Agents that modify chromatin structure (zinc, poly[ADPribose] inhibitors, spermine) can block DNA fragmentation without affecting cell survival. By contrast macrophage-like differentiation by phorbol esters suppresses apoptosis without affecting topoisomerase-induced DNA damage. Better understanding of the apoptotic regulation in the widely used and characterized HL-60 cell line should allow the identification of new mechanisms and parameters of cellular sensitivity and resistance to the cytotoxic activity of anticancer agents.
Leuk Lymphoma 1994 Sep
PMID:Apoptosis induced by DNA topoisomerase I and II inhibitors in human leukemic HL-60 cells. 785

Primary large-cell anaplastic lymphomas (LCAL) presenting in the gastrointestinal tract are rare and sometimes difficult to distinguish from nonlymphoid tumors. Because recognition of these tumors as lymphoma has clinical and prognostic implications for the patient, the diagnostic contribution of genotyping by polymerase chain reaction (PCR) and of immunophenotyping was evaluated in 16 routinely processed samples of gastric and small-intestinal LCALs. Gene rearrangement analysis was done with primers for the immunoglobulin heavy (IgH) and T-cell receptor gamma(TCR gamma) chain. Nine of the 16 cases were assigned to T- or B-lymphoid lineage immunophenotypically. Twelve of the 16 samples had a predominant T- or B-cell clone by PCR. Combination of both methods resulted in lineage assignment of 14 cases (9 T-LCAL, 5 B-LCAL). Two LCAL samples were EBV positive by PCR, one also by immunophenotyping. High expression levels of p53 did not correlate with the presence of EBV or cell lineage. Thus, gene rearrangement studies on routinely processed biopsy specimens by PCR are practical and add to the diagnostic repertoire in cases of gastrointestinal large-cell tumors of immunophenotypically undefined lineage.
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PMID:Large-cell anaplastic lymphoma of the gastrointestinal tract: an immuno- and genotypic study on archival material. 786 Apr 32

Using PCR-SSCP and immunohistochemical analyses, mutations of the p53 tumor suppressor gene were examined in 5 cases of primary malignant lymphoma of the brain (diffuse large cell type). By PCR-SSCP and nucleotide analyses, p53 gene mutations were seen in 2 of the 5 cases. The mutation in one case was a missense G: C-T:A transversion at codon 176 (TGC-TTC; Cys-Phe) which was located in the highly conserved domains and adjoined a previously proposed hot spot codon (codon 175) in various tumors. p53 immunoreactivity was also shown in this case. The mutation in another case was a nonsense G:C-A:T transition at codon 52 (TGG-TGA; Trp-stop codon) leading to a truncated p53 peptide. Thus, these mutations may have actually given rise to serious structural and functional alterations of the p53 protein. These findings suggested that the p53 gene mutation was related with oncogenesis in the primary malignant lymphoma of the brain.
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PMID:Primary malignant lymphoma of the brain: demonstration of the p53 gene mutations by PCR-SSCP analysis and immunohistochemistry. 789 17

In order to assess the clinical role of the MDR1 gene in chronic lymphocytic leukemia (CLL), we determined its expression in the leukemic cells of 39 patients with CLL and compared this with other clinical and laboratory parameters. MDR1 RNA expression was detected in 29 patients. MDR1 RNA transcripts were independent of age, treatment status of the patients and the clinical stage of CLL, but correlated with the white blood cell count and MDR2 RNA transcripts. Expression of the tumor suppressor gene p53 was found in 30 out of 37 patients and was associated with MDR1 RNA expression (P < 0.001). Immunocytochemistry using the monoclonal antibody C219 was performed in 38 patients, and in 28 cases, more than 5% of the leukemic cells were found to express cell surface P-glycoprotein. P-glycoprotein expression correlated with the expression of MDR1 RNA (P = 0.048).
Leuk Lymphoma 1994 Apr
PMID:MDR1 gene expression in chronic lymphocytic leukemia. 791 28

Minute alterations of the p53 tumor suppressor gene and N-ras oncogene were investigated in 106 samples for the p53 gene and 23 samples for the N-ras gene obtained from patients with various types of hematologic malignancies using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct nucleotide sequencing. Mobility shifts suggesting sequence alteration were observed in 9 cases (8.5%) in exons 5 through 8 containing evolutionarily highly conserved regions of the p53 gene by PCR-SSCP; missense point mutations in 3 cases (1 acute myelogenous leukemia (AML), 1 chronic myelogenous leukemia (CML) in the accelerated phase, and 1 CML in the blast crisis), silent point mutation in 1 case (malignant lymphoma), and frame shift mutations due to insertions and deletions causing stop codons in 3 cases (1 AML, 1 CML in the chronic phase and 1 acute lymphoblastic leukemia (ALL)). p53 gene alterations did not always cluster within evolutionarily highly conserved regions, and there were various base change forms in cases with p53 point mutations. p53 mutations were detected in 2 cases out of 4 cases with 17 monosomy. There was no case with p53 gene alteration in myelodysplastic syndrome (MDS) cases. Mobility shifts suggesting sequence alteration were observed in 5 cases (22%) in exon 1 and 2 of the N-ras gene by PCR-SSCP. 3 cases (1 MDS, 1 MDS overt AML and 1 ALL) were detected to contain missense point mutations. However, simultaneous mutations in both the genes were detected in only 2 cases out of 23, thereby indicating infrequent occurrence of concomitant mutation of both the genes in hematologic malignancies. Alterations of the p53 and the N-ras genes are involved in the tumorigenesis, progression and prognosis of at least some cases of hematologic malignancies, in spite that they are relatively infrequent.
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PMID:[Molecular study on minute alterations of the p53 and the N-ras genes in hematologic malignancies]. 792 79

We have characterized a new Epstein-Barr-virus(EBV)-like herpesvirus associated with lymphomas of SIV-infected cynomolgus (Macaca fascicularis) monkeys and propose that this virus is designated herpesvirus macaca fascicularis I (HVMFI). Genomic regions in HVMF1 of potential significance for tumor pathogenesis were analyzed by Southern blotting, PCR and sequencing, and compared with human EBV DNA. Virus from 7 SIV-associated lymphomas and one lymphoma-derived cell line were shown to share homology with the EBNA1- and EBNA2-coding regions of EBV, while some homology to EBV-LMP1 was detectable only at low-stringency hybridization. Homologous regions to the long internal repeat (IR1; BamHI W), the EBER1 and 2 and the latent origin of DNA replication (oriP) could also be demonstrated in HVMF1. These coding regions, except IR1, showed restriction-enzyme maps different from those of EBV. Sequencing of the EBNA5 homologous region of HVMF1 DNA, corresponding to exons W1 and W2, showed 65% homology to the EBV exons W1 and W2, and 80% to the whole region including the intron. Since EBNA5 has been reported to bind tumor-suppressor proteins p53 and Rb in vitro, the HVMF1 homology could be important for the lymphomagenic capacity of this monkey herpesvirus.
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PMID:DNA of lymphoma-associated herpesvirus (HVMF1) in SIV-infected monkeys (Macaca fascicularis) shows homologies to EBNA-1, -2 and -5 genes. 792 31

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold higher levels of MDM2 gene expression than that observed in normal B cells. Immunohistochemical analysis confirmed MDM2 overexpression at the cellular protein level. MDM2 gene overexpression was found more frequently in patients with the low-grade type of lymphoma (56.5%) than in those with intermediate-/high-grade types (10.8%) (P = .001). Moreover, MDM2 overexpression was found significantly more frequently in patients at advanced clinical stages. Simultaneous analysis of p53 gene mutation showed that three patients had both MDM2 gene overexpression and p53 gene mutation. The results of the present study suggest that MDM2 gene overexpression may play an important role in the tumorigenicity and/or disease progression of CLL and low-grade lymphomas of B-cell origin.
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PMID:The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. 794 88

Frequent point mutations of the p53 tumor suppressor gene have been detected in solid tumors but not in acute myelogenous leukemia (AML). The inactivation of the suppressor function of the p53 protein in AML cells may be achieved through the acquisition of a mutant-like conformation. We provide evidence in this report that the p53 protein in AML cells switches to a mutant-like conformation in response to growth factor stimulation, and we propose that the conformation of p53 protein is one of the molecular mechanisms in determining whether the cells proliferate or enter apoptosis. We also show that wild-type p53 with mutant-like conformation is not equivalent to mutant p53 in their stability, which is consistent with the fact they have very different biological activities in the cells.
Leuk Lymphoma 1994 Jul
PMID:Conformational change of p53 protein in growth factor-stimulated human myelogenous leukemia cells. 795 Sep 13

Leukemias and lymphomas occurring in a series of families with Wilms' tumor (WT) are described. One surviving case developed a large cell anaplastic Ki-1 lymphoma at age 20 years, and 23 second- and higher degree relatives were affected. In two instances leukemia/lymphoma occurred in the context of Li-Fraumeni syndrome (LFS) and two other families showed striking clusters of unusual and early-onset malignancies. In several cases, children had genitourinary abnormalities of the type associated with the WT1 gene on chromosome 11p13. Some of these families may provide important subjects for study of WT genes in hematologic disease and lymphomas and for investigation of interaction between different tumor-suppressor genes, e.g., WT1 and other candidate WT genes, and p53.
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PMID:Leukemia, lymphoma, and related disorders in families of children diagnosed with Wilms' tumor. 795 23


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