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)

We investigated chromosome alterations and mutations of the p53 gene in 118 samples from 92 patients with chronic myelogenous leukemia in various clinical phases, i.e., chronic phase, accelerated phase, and blast crisis (BC). Single-strand conformation polymorphism analysis and subsequent nucleotide sequencing disclosed no alteration of the p53 gene in chronic phase (no mutation in 80 samples), while five of 31 BC samples showed point mutations: four in myeloid and one in lymphoid crisis. One of seven accelerated phase samples also showed a p53 gene mutation. Ten of 31 BC samples showed loss of one of the short arms of chromosome 17 (17p) through the formation of isochromosome 17q, i(17q), or unbalanced translocations. Loss of heterozygosity at the p53 locus in the accelerated phase and BC was detected only in two cases with i(17q) but not in seven cases with normal chromosome 17 homologues, suggesting that loss of one p53 allele is rare without cytogenetically detectable loss of a 17p. Among those six samples with p53 gene mutations, five showed loss of a 17p cytogenetically, and only one lymphoid crisis case exhibited normal chromosome 17 homologues. Thus, mutations of the p53 gene were closely associated with myeloid crisis with loss of a 17p (four mutations in ten samples), in contrast to myeloid crisis with normal chromosome 17 homologues (zero in 13) or lymphoid crisis (one in seven). Our results also suggest that alterations of the p53 gene might occur after loss of a 17p during the course of chronic myelogenous leukemia.
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PMID:Frequent p53 gene mutations in blast crisis of chronic myelogenous leukemia, especially in myeloid crisis harboring loss of a chromosome 17p. 142 4

Chronic myelocytic or Ph1-positive acute lymphoblastic leukemias have been analyzed for alterations in a variety of proto-oncogenes and anti-oncogenes implicated in the progression of chronic myeloid leukemia (CML) from its chronic phase to blast crisis. The most frequent genetic change found in disease evolution is an alteration of the p53 gene involving a point mutation, a rearrangement or a deletion. These gene changes are common in myeloid and undifferentiated variants of blast crisis but are usually undetectable in lymphoid leukemic transformants. Other molecular changes also occur in the clonal evolution of CML. The retinoblastoma-susceptibility (Rb) gene is an anti-oncogene. Structural abnormalities of Rb are frequent in all types of human acute leukemia, but are particularly common in Ph1-positive leukemia of lymphoid phenotype including both Ph1-positive ALL and lymphoid blast crisis of CML. Changes in Rb occur early in the transition to blast crisis with loss of Rb protein being the common factor. Mutations in the N-RAS gene also occur, but are rare in typical blast crisis. They are sometimes seen in Ph1-negative myeloid blast crisis. Since changes in the p53 gene are generally associated with progression of disease of a myeloid phenotype and changes in the Rb gene occur more often with a lymphoid phenotype, a particular molecular alteration may influence the character of disease evolution in CML.
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PMID:Molecular mechanisms in the evolution of chronic myelocytic leukemia. 149 27

The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms.
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PMID:[Mutations of the p53 gene in hematologic neoplasms]. 151 57

Mutations of the p53 tumour suppressor gene have frequently been observed in several types of solid tumours and are believed to be implicated in the development of these tumours. To determine the relevance of p53 mutations in haematologic neoplasms, we performed polymerase chain reaction-single strand conformation polymorphism analysis on the p53 gene in 45 patients with various types of haematologic neoplasms. In exons 5-8 containing highly conserved regions, mobility shifts indicating sequence alterations were detected in four of the 45 patients, and subsequent sequencing was performed. A point mutation resulting in a novel stop codon was detected at codon 213 in one of 23 cases of chronic myelogenous leukaemia (one of five cases of blast crisis). Point mutations causing amino acid substitutions were detected in one of four cases of myelodysplastic syndrome at codon 195, one of three cases of adult T-cell leukaemia at codon 281, and one of eight cases of acute lymphoblastic leukaemia at codon 281, and these missense mutations were accompanied by loss of the wild type allele. Patients harbouring these nonsense and missense mutations were in advanced disease stages. These findings suggest that mutational inactivation of the p53 gene is infrequent but is involved in the tumorigenesis of several types of haematologic neoplasms at least in some cases.
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PMID:Mutations of the p53 tumour suppressor gene in haematologic neoplasms. 848 63

Mutations of the tumor suppressor gene p53 are found in a wide variety of human tumors. In hematological malignancies, p53 alterations are involved in the evolution of chronic phase CML to myeloid blast crisis. p53 mutations were also found associated with Burkitt lymphoma (35%) and its leukemic counterpart, L3 type B-cell acute lymphoblastic leukemia (60%). These observations suggest that several common mechanisms are involved in the transformation process of these two hematological disorders.
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PMID:p53 gene alterations in human hematological malignancies: a review. 181 1

The configuration of the P53 tumor suppressor gene was investigated in 43 Chinese patients with chronic myelogenous leukemia (CML), 32 in chronic phase and 11 in blastic crisis. No obvious rearranged DNA band was detected in Southern blot patterns from patients at both stages of the disease. However, P53 gene deletion events were observed in 4 out of 11 cases in blast crisis. This finding was associated with a cytogenetically identifiable chromosome 17p deletion, iso(17q), in only one out of 4 cases.
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PMID:Monoallelic deletions of the P53 gene in Chinese patients with chronic myelogenous leukemia in blastic crisis. 181 2

We tested a population of over 60 patients with chronic myelogenous leukemia (CML) for changes in the structure and expression of the p53 gene, which is located on chromosome 17. Six of 27 (22%) blast crisis samples and 3 of 5 (60%) accelerated phase samples had rearrangements of chromosome 17, whereas only 3 of 42 (7%) chronic phase patients had cytogenetic changes in chromosome 17. There was no loss of heterozygosity during the transition to blastic crisis among seven individuals who were informative for polymorphic probes for regions in or around the p53 gene on 17p. One patient in the chronic phase and one patient in the blastic phase of the 61 CML patients studied exhibited rearrangements of the p53 gene that were detectable by Southern analysis. One p53 allele was rearranged in the chronic phase patient and both p53 alleles were rearranged in the blastic phase patient. The p53 messenger RNA (mRNA) was of normal size (2.8 kb) in chronic phase and blast crisis, and the expression of the p53 gene was at least as high or higher in blast crisis as in the chronic phase of CML. The high incidence of abnormalities of chromosome 17 in blast-crisis CML found in our studies and the discovery of rearrangements of the p53 gene in two CML patients studied suggest that further study with probes for the p53 gene and anonymous polymorphic sites in chromosome 17 should be conducted in CML.
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PMID:Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. 196 14

A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
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PMID:Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. 203 25

DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.
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PMID:The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia. 204 Jun 94

Alterations of the p53 anti-oncogene have recently been found to occur frequently in the blast crisis of chronic myelocytic leukaemia. The p53 gene may be altered by gross structural alterations or by point mutations in the coding sequence. We now report a novel mechanism of gene inactivation in a blast crisis cell line where a mutation in a splice donor site at the 5' end of the fifth intron of the gene interrupts RNA processing and gene expression.
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PMID:A splicing mutation accounts for the lack of p53 gene expression in a CML blast crisis cell line: a novel mechanism of p53 gene inactivation. 222 33


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