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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with a primary immunodeficiency syndrome have an increased risk of the development of a malignancy. Lymphoreticular malignancies are the most common malignancies in these patients. Patients with ataxia telangiectasia (AT) also appear to be at a high risk for the development of non-lymphoid tumors, in particular carcinomas of the gastrointestinal tract and central nervous system tumors. We describe a child with an immunodeficiency and slight neurologic manifestations. During childhood she developed consecutive three primary malignancies.
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PMID:[A patient with an immunodeficiency and consecutively 3 primary malignancies]. 266 72

Individuals with either primary or secondary immunodeficiencies are at high risk to develop not only infections but also malignancy (especially of the lymphoid system). The major focus of this paper is on malignancies that develop in immunodeficiency syndromes, particularly malignancies in naturally occurring immunodeficiencies and following bone marrow transplantation (BMT). As of August, 1986, 514 cases of naturally occurring immunodeficiencies have been registered at the Immunodeficiency Cancer Registry. Overall non-Hodgkin's lymphomas predominate in these patients, accounting for 48.6% of all cases. Non-Hodgkin's lymphoma is the predominant malignancy in ataxia-telangiectasia, common variable immunodeficiency, Wiskott-Aldrich syndrome (WAS) and severe combined immunodeficiency (SCID). The histopathology of the lymphomas differs somewhat in each of the disorders. In WAS, large cell "histiocytic" lymphoma predominates, with most cases having the features of B lymphocytes, including pleomorphic immunocytoma and immunoblastic lymphoma. Non-Hodgkin's lymphoma in SCID also generally has B cell features and in some cases multiple copies of Epstein-Barr virus (EBV) genomic DNA have been found in tumor tissue. In contrast to ataxia-telangiectasia, in which non-Hodgkin's lymphoma is also the predominant neoplasm, the morphology and cell marker characteristics are more similar to those seen in nonimmunodeficient children. The lymphomas in ataxia-telangiectasia are very heterogeneous with representation from all the major histologic subtypes. We have found no relationship between the degree of immunodeficiency and the development of malignancy. Immunodeficiency following BMT, as in naturally occurring immunodeficiencies, appears to predispose patients to the development of lymphoid malignancy, especially for recipients of partially mismatched bone marrow. In Minnesota 8 patients have developed B cell lympho-proliferative disorders (BLPD) following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of immunodeficiency to lymphoid malignancy. 284 Jun 29

Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas.
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PMID:Uterine tumors in ataxia-telangiectasia. 291 Jul 90

Ataxia telangiectasia (A-T) is an autosomal recessive disorder in which patients show an unusual predisposition to lymphoid malignancies including T-cell leukaemia. We compare here the surface phenotypes of fresh and cultured A-T T cells. A total of 17 T-cell cultures from 8 A-T patients are compared with each other and with 5 T-cell cultures from normal individuals. The large, cytogenetically abnormal t(14;14) and t(X;14) clones in 2 of the patients both occurred only in the CD8+ population of T lymphocytes. There was no difference in the rate of growth of A-T T cells in vitro compared with those from normal individuals, although many of the original characteristics of the T cells were lost, including the cytogenetically abnormal clones seen in fresh A-T lymphocytes.
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PMID:A comparison of fresh and cultured T lymphocytes from patients with ataxia telangiectasia using T-cell subset markers and chromosome translocations. 349 96

Ataxia-telangiectasia (AT) is a primary genetic immunodeficiency disease predisposing to cancer. Approximately 40% of patients with AT develop malignancy, usually of the lymphoid system. Increased chromosome breakage in AT leads to rearrangements such as translocations and inversions. The preferred chromosome breakpoints in AT involve genes in the immune system: the immunoglobulin (Ig) gene loci in chromosome bands 2p12, 14q32, and 22q11 and the T cell receptor (TCR) gene loci in chromosome bands 7p13, 7q35, and 14q11. Identical chromosome breakpoints are observed in chromosome rearrangements in normal T cells, Burkitt's lymphoma, and adult T cell leukemia. Molecular analysis of these chromosome rearrangements reveals recombination between an oncogene and Ig or between Ig and TCR. In AT, chromosome rearrangements connect the immune system to lymphoid cancer.
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PMID:Chromosome changes connect immunodeficiency and cancer in ataxia-telangiectasia. 349 17

The wasted mouse, an animal model proposed for the genetically transmitted human disease ataxia telangiectasia (AT), was examined for its biological, cytogenetic and biochemical properties. In affected homozygotes, a marked age-dependent decrease in the ratio of spleen and thymus to body weight, and a slight but significant decrease in the liver to body weight ratio were observed while no such change was found in the kidney. An age-dependent increase was observed in the frequency of both spontaneous and gamma-ray-induced chromosomal aberrations in bone marrow cells of wasted mice. In littermate control mice, neither of these alterations was observed in an age-dependent manner. The activity of a primer activating enzyme, which has been reported to be deficient in AT cells, also decreased with age in spleen cells, but not in liver cells of affected mice. However, alterations in apurinic DNA endonuclease activity were not detected in the developmental stages examined. These data indicate that this mouse mutant may serve as a useful animal model for studying the relationships between DNA repair and lymphoid tissue differentiation.
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PMID:Evaluation of the mouse mutant "wasted" as an animal model for ataxia telangiectasia. I. Age-dependent and tissue-specific effects. 370 98

Certain rare human diseases with autosomal recessive mode of inheritance are associated with a greatly increased cancer frequency which may reflect specific defects in DNA repair or replication. These disorders include xeroderma pigmentosum, ataxia-telangiectasia, Fanconi's anaemia and Bloom's syndrome. Cells from individuals with Bloom's syndrome usually grow slowly in culture and exhibit increased chromosomal breakage and rearrangement, an elevated frequency of sister chromatid exchanges, retarded rates of progression of DNA replication forks, delayed conversion of replication intermediates to high-molecular-weight DNA, and slightly increased sensitivity to DNA-damaging agents. Several of these features are also characteristic of Escherichia coli and yeast mutants with a defective DNA ligase. In this investigation we show that one of the two DNA ligases of human cells, ligase I, is defective in a representative lymphoid cell line of Bloom's syndrome origin.
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PMID:DNA ligase I deficiency in Bloom's syndrome. 380 31

The current concepts of the mechanisms of initiation and regulation of the proliferative response of lymphoid cells underlie a series of research performed by the authors. Using the modern methods an attempt was made to analyze comprehensively the causes of its lowering in patients with congenital immune deficiency (ataxia-telangiectasia, the Louis-Bar syndrome). It was established that irresponsiveness of the patients' cells to mitogens is not associated with the inability of these cells to interact with mitogen, to produce the growth factor of T cells or adsorb it on their membrane. It is suggested that the derangement is likely to be connected with the blockade of the postmembrane component of the proliferation trigger. It is also assumed that the analysis of the low proliferative response employed by the authors can be successfully used for other pathologies.
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PMID:[Staged analysis of the lowered proliferative response of human lymphocytes to mitogens]. 387 3

Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid cells, suggesting that the capacity to repair the induced DNA lesion is present.
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PMID:The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells. 617 10

Cytogenetic damage was investigated in long term lymphoid cell lines derived from normal individuals, patients with Fanconi's anemia (FA), ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and FA heterozygotes. The cell lines were exposed to various concentrations of four chemical clastogens, including the alkylating agents diepoxybutane, mitomycin C, and nitrogen mustard, as well as the antitumor glycopeptide bleomycin. The FA cells exhibited chromosomal hypersensitivity to all four clastogens and could be distinguished from the other genotypes. AT cells were identified by bleomycin, while FA heterozygotes could not be reliably detected. Discriminant function analysis was used to describe the cytogenetic response to the various clastogens. This method might prove useful for evaluation and classification of multivariate chromosome breakage studies.
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PMID:The cytogenetic response of Fanconi's anemia lymphoblastoid cell lines to various clastogens. 618 57


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