Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53,000 dalton protein called p53, was noted to be mutated in human cancer in 1987. Further studies have shown that p53 is a tumor suppressor gene which may be one of the most frequently altered genes in cancer of all types. These alterations include interactions with viral antigens, coding mutations and inactivating rearrangements. Accumulating evidence suggests that p53 acts by binding DNA and activating transcription. Expression of p53 after transfection with a constitutive promotor, blocks cellular proliferation and leads to an apoptotic cell death. In normal cells, p53 expression is induced by irradiation; this has led to the hypothesis that p53 acts to inhibit replication during genetic repair. Cells which lack p53 are more prone to develop amplification. Mice lacking p53 are born normal but develop cancer after a lag of months, this suggests that p53 is not an initiating mutation in cancer, but probably a late event.
Leukemia 1993 Aug
PMID:P53 mutations in human cancer. 836 Dec 26

In her 8 1/2 years of life, a girl with neurofibromatosis type 1 (NF1) developed four sequential primary malignant neoplasms: Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and acute myeloid leukemia. The last three tumors were characterized by chromosomal abnormalities non-randomly associated with that particular disease. There was no evidence of germline p53 mutation or of mutation of p53 in the last two tumors. We hypothesize that an unusual mutation of the NF1 gene in this child promoted growth in tissues where the normal or mutated NF-1 gene product is usually silent or growth inhibitory.
Leukemia 1993 Jun
PMID:Sequential development of Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and myeloid leukemia in a child with type 1 neurofibromatosis: a clinical and cytogenetic case report. 838 72

The Cas-Br-E murine leukemia virus is a non-defective retrovirus that induces non-T-, non-B-cell leukemias in susceptible NIH/Swiss mice. A collection of tumors was examined for genomic DNA structure and RNA expression of known or putative proto-oncogenes and one tumor-suppressor gene, with the aim of identifying genes involved in Cas-Br-E-induced non-T-, non-B-cell leukemogenesis. Fli-1, p53, and Evi-1 were found to be rearranged in 72%, 23%, and 18% of the tumors, respectively, whereas no DNA alteration were detected for c-myc, c-myb, Pim-1, Evi-2, and EpoR genes. Evi-1 rearrangements are rarely associated with p53 or Fli-1 alterations. However, rearrangements of these last two genes are very often associated within the same tumor. Moreover, patterns of coordinated expression of critical cell growth-regulating genes are consistently associated with specific tumor types. These data suggest that Cas-Br-E can induce two types of hematopoietic neoplasias by different mechanisms.
Leukemia 1993 Jul
PMID:Expression and DNA rearrangement of proto-oncogenes in Cas-Br-E-induced non-T-, non-B-cell leukemias. 839 16

We screened 23 cases of Philadelphia chromosome (Ph1)-positive acute leukemia (Ph1AL) for loss of a chromosome 17p and mutations in exons 2 to 11 of the p53 gene by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Loss of a distal part of chromosome 17p including loss of a whole chromosome 17 emerged in three cases, among which two were Ph1-positive acute lymphoblastic leukemia (Ph1ALL) with point mutations within the highly conserved region of the p53 gene. Another case of Ph1-positive acute myelogenous leukemia (Ph1AML) also exhibited a p53 point mutation in company with loss of normal p53 allele, although showing normal chromosome 17 homologues. We also performed Southern blot hybridization analysis to examine p53 gene rearrangements in 13 cases of Ph1AL. We found a rearrangement in one case of Ph1ALL and a loss of heterozygosity (LOH) at the p53 locus without any rearrangement in another Ph1ALL. Both cases showed no abnormality within the entire coding region by SSCP analysis. Thus, p53 gene alterations were commonly involved in Ph1AL with loss of a 17p (two point mutations in three cases), while rarely in cases with normal chromosome 17s (one point mutation in 20 cases and one rearrangement in 13 cases). Rare p53 gene alterations in Ph1AL may therefore be related to low incidence of loss of a chromosome 17p.
Leukemia 1993 Oct
PMID:p53 gene mutations and loss of a chromosome 17p in Philadelphia chromosome (Ph1)-positive acute leukemia. 841 16

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.
Leukemia 1993 Oct
PMID:Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations. 841 23

Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.
Leukemia 1993 Oct
PMID:In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection. 841 24

Rearrangements of the c-abl protooncogene and the bcr-gene are found in > 90% of patients in chronic phase of chronic myelogenous leukemia (CML). The molecular events leading to blast crisis, however, have not been well characterized. Gross alterations of the p53 gene have been detected in 30% of patients with blast crisis. Since point mutations in the p53 gene appear to be important in the process of transformation in many epithelial tumors, we looked for these mutations in the critical regions of the p53 gene (exons 4, 5, 6, 7, and 8). We used the polymerase chain reaction (PCR), direct sequencing, differential PCR, and single strand conformation polymorphism (SSCP) analysis to detect mutations of the p53 gene in samples from 21 patients with CML blast crisis. Two of 21 patients exhibited an intragenic deletion or rearrangement in p53. In addition, these patients were homozygous for the mutant p53 allele. No mutations were found in the p53 gene of the remaining 19 patients. However, sequencing of the CML blast crisis cell line, K562, revealed an insertion of a C at base position 956 within the fifth exon, causing a frame shift mutation and an early translational stop at codon 148. We conclude that, in contrast to solid tumors, mutations in exons 4-8 of p53 are not frequently seen in primary samples from CML blast crisis. However, deletions and/or rearrangements within the p53 gene do occur and may contribute to the progression from chronic phase to blast crisis in a limited number of patients with CML.
Leukemia 1993 Apr
PMID:Genetic alterations in the p53 gene in the blast crisis of chronic myelogenous leukemia: analysis by polymerase chain reaction based techniques. 846 38

Mutations in the p53 tumor suppressor gene occur with a frequency of 12.5% in lymphoid malignancies. The viral-associated diseases, Adult T-cell Leukemia (ATL) and Burkitt's lymphoma, showed higher p53 mutation frequencies of 24% and 41%, respectively. Mutations occurred in the highly conserved regions of the p53 gene. Two new hot spots for mutation were noted in exon 7 at codons 239 and 245. The spectrum of p53 mutations differs among different cancers. Transition mutations occurring in colon and brain tumors also predominated in the majority of the lymphoid malignancies. However, B-cell chronic lymphocytic leukemia (B-CLL) and non-Hodgkin's lymphoma (NHL) had an unusually high frequency of G to T transversions. Among carcinomas of the lung, liver, breast and esophagus there is also a high frequency of G to T transversions. The differences in mutation spectra between different lymphoid diseases may be due to differences in mutagenic factors or differences in the biological properties of the p53 protein in different lymphoid compartments. Mutation of the p53 gene is associated with advanced stage of lymphoid disease and poor prognosis. For B-CLL disease, p53 mutations are associated with drug resistance. Overexpression of the bcl-2 protein is also associated with a block in apoptosis. Resistance to apoptosis could be a general mechanism for drug resistance in B-CLL and other lymphoid diseases.
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PMID:P53 gene mutations in lymphoid diseases and their possible relevance to drug resistance. 858 Jul 89

Human T cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T cell leukemia (ATL) transforms human T cells in vitro and in vivo. Tax, the major transactivator of HTLV-I is critical for the initial events involved in transformation, however, the later steps required for progression from an IL-2 dependent state to one of IL-2 independence remain to be clarified. We investigated the potential role of p53 protein in this process employing several IL-2 dependent and independent HTLV-I transformed cell lines. All cell lines examined were found to be wild-type in the p53 coding region usually associated with inactivating mutations using RT-PCR-SSCP analysis and DNA sequencing. Levels of p53 protein were consistently higher in IL-2 independent lines compared to IL-2 dependent ones. Lack of functional p53 activity was observed only in IL-2 independent cell lines using a transfection assay with a B-galactosidase reporter gene construct responsive to wild-type p53 protein. Increased steady state levels of wild-type p53 protein associated with its functional inactivation appear to be linked to the loss of IL-2 dependent growth in HTLV-I transformed lymphocytes.
Leukemia 1995 Dec
PMID:Functional inactivation of wild-type p53 protein correlates with loss of IL-2 dependence in HTLV-I transformed human T lymphocytes. 860 20

In this study, we investigated the responses of the T cell leukaemia cell line, CCRF-CEM, and a vincristine-resistant subline, CEM/VCR R, to the induction of cell death by serum withdrawal. This treatment was used to overcome any contribution of P-glycoprotein-mediated drug resistance to the responses of the CEM/VCR R cells. Following serum withdrawal both cell lines exhibited typical apoptotic responses including morphological changes and nucleosomal cleavage of the DNA. However, using several different assays for cell death the CEM/VCR R cell line was shown to undergo apoptosis at a slower rate than the parental CCRF-CEM cell line. Expression of c-Myc, Bcl-2 and p53 was found to be similar in both cell lines, discounting involvement of these proteins in the observed difference in apoptotic response. Given our previous finding that reorganisation of tubulin is involved in apoptosis, we examined the expression of alpha-, beta- and acetylated alpha-tubulin in the parental and resistant lines. The CEM/VCR R cell line had altered tubulin expression when compared to that of the CCRF/CEM line. Transnuclear microtubule networks were observed in log phase CEM/VCR R cells. In addition, increased expression of the acetylated form of the alpha-tubulin isotype suggested that a more stable microtubule network was present in the CEM/VCR R cells. These findings imply that the drug-resistance phenotype in the CEM/VCR R cells may involve the suppression of apoptosis, and that the development of an altered microtubule network may contribute to this suppression.
Leukemia 1996 Mar
PMID:Resistance to apoptotic cell death in a drug resistant T cell leukaemia cell line. 864 60


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