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

Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. We report a 51/2 year old boy who had undiagnosed ataxia telangiectasia when he presented with acute lymphoblastic leukaemia. He subsequently developed a chemoradiation induced leukoencephalopathy after conventional central nervous system prophylaxis.
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PMID:Leukoencephalopathy after prophylactic radiation for leukaemia in ataxia telangiectasia. 273 Jan 36

Molecular analysis of somatic cell hybrids derived from T cells carrying a t(7;14)(q35;q32) chromosomal translocation from a patient with ataxia telangiectasia and T cell leukemia indicates that the breakpoint on chromosome 14 is proximal to the IgH locus and to the D14S1 locus, while the breakpoint on chromosome 7 involves the T cell receptor beta chain locus immediately 5' to J beta 1.5 on chromosome 7. The separation of V beta and C beta observed in somatic cell hybrids defined the orientation of the T cell receptor beta chain locus on chromosome 7 where the V beta genes are centromeric and the C beta genes are telomeric. A novel chromosomal alteration, undetected cytogenetically, was revealed as being an inversion with duplication of the distal band of chromosome 14q32. The importance of the 14q32 region in the leukemogenic process is discussed.
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PMID:Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. 325 92

At the beginning of this century Theodor Boveri predicted that specific chromosome changes would be found to have a causal role in neoplasia. We are now beginning to acquire the evidence to substantiate this hypothesis. The evidence comes from two particular sources, (i) genetic environmental interactions and (ii) specific constitutional chromosome aberrations. Cancer incidence varies throughout the world. This is often due to the interaction of an environmental agent with a genetically varied population. Using UV and ionising radiation as examples it is argued that some individuals are more susceptible to genetic damage by these agents. Moreover, the genetic lesions which are caused by these agents are now being shown to be relevant to cancer. In the radiosensitive syndrome ataxia-telangiectasia for example, specific chromosome rearrangements have been defined which seem likely to be directly involved in the development of leukaemia in these patients. The second line of evidence comes from the study of patients who have constitutional chromosome abnormalities associated with susceptibility to specific cancers. It has now been shown that these chromosome changes mark the location of genes which are involved in the development of cancer and that these same loci are also important in the non-familial forms of these diseases. Thus we are beginning to understand for the first time the mechanistic pathway that leads from environmental agents, through chromosome damage, to the alteration of specific genes which control the neoplastic process.
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PMID:Chromosomes and cancer families. 333 94

Peri- and paracentric inversions are observed in human leukocytes at various rates. Four categories are proposed, in relation to the frequency of occurrence, although it may vary with time for a same inversion. Category 1 corresponds to isolated, thus non recurrent inversions. Category 2 (f congruent to .001) corresponds to inv(14)(q12qter) and inv(7)(p14q35) in individuals with presumably normal genetic constitution. Category 3 (f congruent to .01) corresponds to inv(7)(p14q35) in patients affected by ataxia telangiectasia (AT). This inversion, when it is frequent, indicates an abnormal genetic constitution, radiation sensitive and predisposing to cancers. Finally, category 4 (f greater than or equal to .1) corresponds to inversions existing in precancer or in cancer clonal cells: inv(14)(q11.2q32.2) in AT patients affected by a T-cell hemopathy, inv(14)(q12qter) in chronic T-cell lymphocytic leukaemia, and inv(16)(p13q22) in acute myelomonocytic leukaemia with abnormal eosinophils. The prognostic and diagnostic interests of these inversions is discussed.
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PMID:Acquired inversions in human leucocytes. 349 76

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

Cell line ML-1 was established from a myelogenous leukemia of an RFM mouse. The ML-1 cells and in vitro normal mouse bone marrow cells were analyzed to determine if there was a differential sensitivity to X-ray-induced chromosome aberrations in G1 cells and/or differences in postirradiation cell cycle progression. Cells identified as being in G1 at the time of irradiation by their staining pattern after replication in 5-bromodeoxyuridine were analyzed for all types of chromosomal aberrations following X-ray doses of 0.5, 1.0, 1.5, and 2.0 Gy. ML-1 cells showed a greater sensitivity to the induction of both chromosome-type aberrations (dicentrics and terminal deletions) and chromatid-type aberrations (exchanges and deletions) compared to normal mouse bone marrow cells, which only contained chromosome-type aberrations. The presence of chromatid-type aberrations in the ML-1 cells and not normal bone marrow cells suggested a differential progression through the cell cycle for the two cell types after irradiation. Mitotic index and flow cytometric analyses were performed and showed that both cell types have a delay in progression from G2 into mitosis, but only the normal mouse bone marrow cells have a delay in progression from G1 into S, as well as delayed progression through the S phase following X-irradiation. These results indicate that the ML-1 leukemia cells have an increased radiosensitivity. This may be due to a defect in their ability to respond to DNA damage as evidenced by their lack of a G1- and S-phase delay which allows normal cells an increased time to repair DNA damage before replication. These same characteristics have been observed in ataxia telangiectasia cells and may well represent a general feature of cells with increased radiosensitivity.
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PMID:Differential sensitivity of a mouse myeloid leukemia cell line and normal mouse bone marrow cells to X-ray-induced chromosome aberrations. 386 3

Three gene families that rearrange during the somatic development of T cells have been identified in the murine genome. Two of these gene families (alpha and beta) encode subunits of the antigen-specific T-cell receptor and are also present in the human genome. The third gene family, designated here as the gamma-chain gene family, is rearranged in murine cytolytic T cells but not in most helper T cells. Here we present evidence that the human genome also contains gamma-chain genes that undergo somatic rearrangement in leukaemia-derived T cells. Murine gamma-chain genes appear to be encoded in gene segments that are analogous to the immunoglobulin gene variable, constant and joining segments. There are two closely related constant-region gene segments in the human genome. One of the constant-region genes is deleted in all three T-cell leukaemias that we have studied. The two constant-region gamma-chain genes reside on the short arm of chromosome 7 (7p15); this region is involved in chromosomal rearrangements identified in T cells from individuals with the immunodeficiency syndrome ataxia telangiectasia and observed only rarely in routine cytogenetic analyses of normal individuals. This region is also a secondary site of beta-chain gene hybridization.
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PMID:Human gamma-chain genes are rearranged in leukaemic T cells and map to the short arm of chromosome 7. 387 97

This paper reports the occurrence of renal cell carcinoma, hepatoma and malignant hepatic mixed tumor in a 22-year-old male with ataxia-telangiectasia (AT). Incidence of various malignant neoplasms is high in the patients with AT. The majority of these are lymphoreticular tumors and leukemia, and epithelial tumors are rare. This report is the first case with renal cell carcinoma and the second with hepatoma. The reason for a low incidence of epithelial tumors in AT is still obscure. It is possible that as the result of abnormal aging the tumors expected in the aged will occur in longer survivors with AT.
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PMID:Ataxia-telangiectasia with renal cell carcinoma and hepatoma. 625 35

Adult T-cell leukemia virus (ATLV) is a human retrovirus closely associated with adult T-cell leukemia. The integrated provirus DNA and cDNA from virion RNA were molecularly cloned and their structures were analyzed. Clone lambda ATM-1 of an integrated provirus DNA in the MT-1 cell line, established from adult T-cell leukemia cells by cocultivation with cord lymphocytes, contained DNA about 13,000 base pairs (bp) long and long terminal repeats (LTR) at both ends of the viral sequence that were about 8,000 bp long. These two LTR sequences were linked to cellular sequences with direct repeats of 7 bp. Each LTR consisted of 754 bp including inverted repeats of 2 bp at the ends and the T-A-T-A-A box, characteristics in common with those of LTRs of other known retroviruses. Adjacent to the 5' LTR there was a sequence identical to the tRNAPro binding site in murine leukemia virus, suggesting that tRNAPro is a primer for reverse transcription of the viral genome. From these structural features, the mechanism of ATLV replication was suggested to be the same as that of other known animal retroviruses. However, the length of the small terminal repeats at the ends of the RNA genome, 228 +/- 1 bases, is much longer than the lengths, up to 80 bases, of those in avian, mouse, or primate retroviruses so far analyzed. These findings suggest that ATLV should be classified in a distinct group of retroviruses with bovine leukemia virus which also makes unusually long strong-stop cDNA.
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PMID:Human adult T-cell leukemia virus: molecular cloning of the provirus DNA and the unique terminal structure. 629 64

A possible causal association between chromosome structural change and neoplastic transformation has long been mooted, particularly since chromosomal changes occur frequently in the cells of a variety of malignancies. Only in recent years, however, has the evidence in support of this contention begun to appear convincing, and this has followed from the application of developments in cytogenetic techniques. The advent of methods for revealing specific bands in the human metaphase complement has enabled all the chromosomes and many chromosomal regions to be unambiguously identified, and the recent application of prophase banding methods gives further improvements in resolution. With these techniques, specific constitutional chromosomal deletions or translocations have been discovered in inherited cases of retinoblastoma (del.13q14), Wilms' tumour with aniridia (del.11p13) and renal-cell carcinoma (t(3:8) (p21:q24)), in which each of the chromosomal changes appears to be a dominant factor in inheriting a predisposition to a tissue-specific tumour. A heritability for cancer predisposition is also associated with the inherited chromosomal instability syndromes of Bloom's, Fanconi's anaemia and ataxia telangiectasia, although specific chromosomal changes have not been reported to be associated with the neoplasms in such individuals, except in some cases of lymphoma and leukaemia in ataxia telangiectasia. Specific chromosomal translocations have, however, been recorded in a variety of malignancies, with a particular involvement of chromosomes 22, 14, 8, 15, 17 and 21. However, although many hundreds of patients with the specific 9/22 rearrangement seen in chronic myeloid leukaemia and also those with the 14/8 rearrangement in Burkitt's, and other, lymphomas have been described, no single case in which these rearrangements were present as constitutional changes has been reported. The possible nature of the changes seen at the cytogenetic level in terms of gene content of the chromosomes involved is discussed.
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PMID:Cytogenetics of heritability in cancer. 629 35


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