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

Five patients with primary immunodeficiency and cancer are presented. Two children with ataxia-telangiectasia developed acute lymphoblastic leukemia and malignant lymphoma of B-like origin with chromosome damage and unusual prevalence of antibodies to E.B.V. early antigen. A bone sarcoma occurred in a patient with common variable hypogammaglobulinemia. At least two infants who died with severe combined immunodeficiency had at autopsy congenital myelomonocytic leukemia and malignant lymphoma. These cases indicate the high risk for development of cancer in patients with primary abnormalities of the immune system and suggest the heterogeneity and complexity of pathogenic mechanisms.
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PMID:[Primary immunologic deficiencies and cancer. 5 anatomo-clinical case reports]. 657 32

Lymphocyte and neutrophil locomotion were studied in 23 patients with well defined, primary immunodeficiencies. These included eight patients with common variable immune deficiency, three patients with X-linked agammaglobulinaemia, two patients with the Wiskott-Aldrich syndrome, three patients with ataxia telangiectasia, three patients with immunodeficiency and normal serum immunoglobulin concentrations, one patient with immune deficiency and hyper-IgM syndrome, two patients with Job syndrome and one patient with a granulocyte adherence defect. Random and stimulated lymphocyte and neutrophil migration were evaluated. C5a and casein were used to stimulate lymphocyte migration and C5a and formyl-methionyl-leucyl-phenylalanine (f-MLP) were used to stimulate neutrophil migration. Significantly depressed lymphocyte migration in response to casein and C5a was observed in patients with common variable immune deficiency, patients with immune deficiency and normal immunoglobulin concentration, and patients with Job syndrome. No consistent defect in lymphocyte locomotion was observed in the other patients studied. Neutrophil migration in response to C5a and f-MLP was depressed in Job syndrome, the patient with a granulocyte adherence defect, one of the six patients with common variable immune deficiency and none of the remaining patients. No significant correlation of skin test reactivity and lymphocyte migration was noted, but a correlation between the degree of lymphocyte proliferation in response to phytohaemagglutinin and lymphocyte migration in response to casein was observed. The results presented indicate that aberrations in lymphocyte migration occur in several types of immunodeficiency diseases and that defects in lymphocyte and neutrophil migration can occur simultaneously or totally independent of each other.
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PMID:Abnormalities of lymphocyte locomotion in immunodeficiency disease. 661 60

This paper referred to primary immunodeficiency diseases (PID)-malignancy association in autopsy cases in Japan. The occurrence of malignant neoplasms almost centered upon ataxia-telangiectasia among PID in Japan. It seems to be due to extremely shorter life span in Japanese patients with PID except for in those with ataxia-telangiectasia, compared with that in European and American patients. Most of the malignant neoplasms seen in Japanese patients with PID were epithelial and were seen mostly in older patients, while lymphoreticular tumors were rare. Gastric cancer was the most frequent of the epithelial tumors.
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PMID:Immunodeficiency-malignancy association at autopsy in Japan. 665 Jan 70

A histologic review was undertaken of 35 lymphoreticular disorders that developed in primary immuno-deficiency patients from the Immunodeficiency Cancer Registry. Twenty-one (60%) of the lesions were non-Hodgkin's lymphomas: these included eight B-immunoblastic sarcomas. Eight (23%) of the lesions were Hodgkin's disease, with a high frequency of lymphocytic depletion type in an unusually young age group. Three lesions (8.5%) represented abnormal proliferative processes, which could not be definitely categorized as either benign or malignant. There were only two acute lymphoblastic leukemias (6%). Differences were found between lymphomas arising in Wiskott-Aldrich syndrome and those occurring in ataxia-telangiectasia; this suggests that different pathogenetic mechanisms might operate in their development. The lymphomas in Wiskott-Aldrich syndrome were all of non-Hodgkin's type, predominantly B-immunoblastic sarcomas, and presented as localized extranodal infiltrates. The lymphomas in ataxia-telangiectasia were either Hodgkin's disease, mostly of lymphocytic depletion type, or non-Hodgkin's lymphomas of the histologic subtypes associated with 14q translocations.
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PMID:Lymphoreticular disorders in primary immunodeficiencies: new findings based on an up-to-date histologic classification of 35 cases. 696 49

Comparison of the strikingly different distributions of types of cancer that occur in the genetic disorders that feature chromosome instability raises several interesting points. (a) Bloom's syndrome: the distribution suggests that many of the cancers that occur with regularity in the general population just occur more commonly and at an earlier age. (b) Ataxia telangiectasia: cancers of many types are increased in frequency, but lymphoreticular cancers are exceptionally common, the case also in several other genetically determined immunodeficiency disorders. Both Bloom's syndrome and ataxia telangiectasia share defective immunity as a major clinical feature, but the respective roles, if any, of it and of chromosome instability in producing the cancer predispositions are unknown. (c) Fanconi's anemia: cancer apparently has become common only recently. The types and distribution which occur are unusual. Fanconi's anemia cells have been shown to be hypertransformable by oncogenic virus and to be defective in handling certain types of DNA damage (as well as to manifest chromosome instability) so that the recent increase in cancer incidence is both surprising and unexplained. The degree of cancer proneness of Fanconi's anemia per se, untreated by modern methods, must at present be considered unknown. (d) Xeroderma pigmentosum: the cancer predisposition apparently extends only to cells which receive solar damage, i.e., to skin and eye. This would not have been predicted in view of the fact that the cellular mechanism is defective for repairing DNA damage produced not just by sunlight but also by certain classes of chemical carcinogens.
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PMID:Chromosome-breakage syndromes: different genes, different treatments, different cancers. 701 10

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by telangiectasia, progressive ataxia, sinopulmonary infections and a combined immunodeficiency (usually consisting of IgA deficiency, IgE deficiency, IgG2 and IgG4 deficiency and a disturbed T cell immunity). The alpha-fetoprotein level is elevated. Cytogenetic studies reveal a very specific chromosome instability with multiple chromosome 7 and/or 14 rearrangements (preferential breakpoints 14q32, 14q12, 7q35 and 7p12). X-ray hypersensitivity is one of the hallmarks of the disease. Nijmegen Breakage Syndrome (NBS), an autosomal recessive disorder with some features of AT, was first reported in 1981. At this moment at least 19 patients have been recognized. Clinical symptoms are microcephaly from birth, a peculiar face, growth retardation, repeated respiratory tract infections and renal abnormalities. Immunological, cytogenetic and cell-biological findings in NBS are identical to AT. However, alpha-fetoprotein levels are not increased. A tendency toward malignancy has been demonstrated in both syndromes. Recently, we encountered three patients with variants of these syndromes.
Immunodeficiency 1993
PMID:Variants of Nijmegen breakage syndrome and ataxia telangiectasia. 751 25

Common variable immunodeficiency and ataxia-telangiectasia with immunodeficiency are both well recognized syndromes which occur in children. The aetiological factors responsible for both these conditions have yet to be defined clearly. The clinical and laboratory features in two siblings, one with common variable immunodeficiency and the other with ataxia-telangiectasia, are presented. This is the first report of these two entities occurring in siblings.
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PMID:The occurrence of ataxia-telangiectasia and common variable immunodeficiency in siblings: case report. 751 39

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.
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PMID:HCV infection in patients with primary defects of immunoglobulin production. 755 76

The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL). It is also involved in T-acute and -chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11. Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation.
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PMID:TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia. 766 82

Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving cerebellar degeneration, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. A-T is heterogeneous, and the majority of A-T cases are associated with two complementation groups, A and C. The ATA and ATC loci are closely linked at chromosome 11q22-q23. Recombination mapping and linkage disequilibrium analysis have confined both loci between the markers D11S1817 and D11S927, spaced approximately 3.5 Mb apart. Isolation in yeast artificial chromosomes of the genomic segment defined by these loci is essential to identify the gene or genes containing the ATA and ATC mutations. A YAC contig spanning 4.5 Mb, which includes the D11S1817-D11S927 interval, was constructed using two whole genome libraries (ICRF and St. Louis), and a chromosome 11-specific library. Construction of this contig was expedited by prior generation of a region-specific ICRF sublibrary using Alu-PCR products derived from a radiation hybrid. The contig was expanded further by screening the libraries with Alu-PCR products derived from YAC clones and with STSs from YAC ends. YAC clones were aligned by fingerprinting with moderately repetitive probes.
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PMID:A YAC contig spanning the ataxia-telangiectasia locus (groups A and C) at 11q22-q23. 769 44


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