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

Among 2966 acute leukemia, 26 familial cases were reported. Leukemia occured mainly in the first relative individuals and particularly in the sibship. The relative risk for a sib of leukemic patient is four time more than for random people. Leukemia was often similar among patients of the same family and the onsets of the disease occured approximatly at the same age whatever the time between the dates of diagnosis. Twins with leukemia were often monozygotous. Relative risk of leukemia among twins, decreases according to the age: the probability of leukemia for a twin is: (a) 100 p. cent if the other twin is leukemic before 1 year old; (b) 15 p. cent between 1 to 4 years old and (c) similar to other sib after 4 years old. Among chronic leukemias, only chronic lymphocytic leukemia seems to have a genetic background for susceptibility. Some familial diseases (congenital aplastic anemia, Bloom's disease, Ataxia telangiectasia) or congenital diseases (Down's syndrome) increase the risk of leukemia.
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PMID:[Familial leukemia (author's transl)]. 66 77

Ataxia telangiectasia is a rare inherited and progressive neurological disorder in which patients show an unusual predisposition to T-cell leukaemia. We report here observations on a patient with a large cytogenetically abnormal clone showing a single t(X;14)(q28;q11) translocation which conferred a proliferative advantage on the cells. The further evolution of this clone to cytogenetically more complex clones of lymphocytes was seen in the patient. She subsequently developed a rapidly progressing T-cell leukaemia, with a CD4+CD8+ T-cell phenotype, about five years after the first appearance of additional chromosome translocations in the clone cells.
Leukemia 1992 Sep
PMID:Development of T-cell leukaemia in an ataxia telangiectasia patient following clonal selection in t(X;14)-containing lymphocytes. 151 8

Ataxia-telangiectasia (A-T) is a syndrome that has an extremely high incidence of cancer. Patients with the disease are homozygous for a mutant gene, the A-T gene, located at 11q23. Of these individuals, 30-40% develop cancer. Of these cancers, 80% are lymphoid. Those heterozygous for the A-T gene also have an increased frequency of cancer, the most notable being the 6.8-fold increase of breast cancer in females carriers. The syndrome is characterized cytogenetically by increased nonrandom chromosome breaks and rearrangements in lymphocytes involving the sites of the immunoglobulin and T-cell receptor genes. Clones of cells having the same rearrangements are often present in the blood of the A-T patients and if the rearrangements involve certain sites, especially a locus within 14q32, the propensity to progress to a malignant transformation is great. Sequencing the A-T gene and ascertaining its function should contribute significantly to our understanding of the molecular mechanisms underlying cancer susceptibility.
Leukemia 1992
PMID:Cancer susceptibility in ataxia-telangiectasia. 154 42

A 12-year-old male patient with ataxia telangiectasia developed an acute lymphoblastic leukemia of T-cell phenotype. The lymphoblasts showed uniform surface expression of CD3, CD7, CD8, and T-cell receptor (TCR) alpha/beta chains, positive immunofluorescent staining of terminal deoxynucleotidyl transferase, complex cytogenetic aberrations including t(14;14) (q11;q32) and unique rearrangements of TCR beta and gamma chain genes, indicating the clonal expansion of leukemic cells. CD25 expression could be readily induced on the leukemic cells by mitogenic stimulation, followed by CD71 expression, but interleukin-2 production and subsequent proliferation in response to mitogens were subnormal.
Leukemia 1991 Jan
PMID:Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia. 199 61

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
Leukemia 1988 Dec
PMID:Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients. 284 95

We report a new case of ataxia-telangiectasia (AT) and acute lymphoblastic leukemia (ALL) and review all 21 known cases of AT and ALL. Leukemia in these patients is associated with a male predominance, age older than 10 years at diagnosis, a white blood cell count higher than 50,000 mm3, and a fatal course. Four patients have been reported who developed T-cell leukemia, 3 null-cell leukemia and 1 B-cell leukemia. The AT-ALL patients appear to be at risk for infections related to their immunodeficient status and ALL chemotherapy. In addition, neurologic deterioration has been noted during the early phase of therapy.
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PMID:Ataxia telangiectasia and acute lymphoblastic leukemia: report of a case. 695 May 88

T cell clones in patients with ataxia telangiectasia (AT) and T cell prolymphocytic leukemia (T-PLL) have identical chromosome abnormalities, namely inv(14)(q11q32), t(14;14)(q11;q32) and t(X;14)(q27;q11). In T-PLL and AT developing T cell leukemia, the above abnormalities occur frequently together with trisomy for 8q. We postulated that the additional abnormalities of chromosome 8, where the c-myc oncogene is mapped to 8q24, may play a role in the development of overt leukemia. DNA analysis using the CD1A c-myc probe did not reveal rearrangements of the c-myc gene by Southern blotting. We have used a monoclonal antibody for the c-myc protein to investigate the level of expression in 11 patients with T-PLL and two with Sezary cell leukemia and compared it with levels seen in normal lymphocytes. Significantly higher levels were observed in patients compared with controls (P < 0.0001). The highest levels of c-myc were seen in eight cases with trisomy for 8q resulting from an i(8q). One patient was investigated before and after treatment. In the active state, c-myc showed a level of 64.36 units (range 20-200). After treatment a residual population of malignant cells showed a c-myc level of 155 (range 90-280). This study suggests that the increased expression of c-myc as a result of trisomy for 8q may have a role in the pathogenesis of de novo T-PLL and T cell leukemia supervening AT and that there may be a correlation between c-myc levels and resistance to therapy.
Leukemia 1995 Oct
PMID:Expression of c-myc oncoprotein in chronic T cell leukemias. 756 12

A t(X;14)(q28;q11) translocation was present for many years in T cells in two patients with ataxia telangiectasia (A-T), who subsequently developed T-prolymphocytic leukemia. We describe here the relationship between the translocation breakpoints in these patients with respect to two recently described genes, c6.1A and c6.1B, on Xq28 which are transcribed in opposite directions from the same CpG island. In our first patient, the Xq28 breakpoint disrupts the c6.1A gene which is consequently transcribed as a fusion mRNA with the TCR C alpha chain gene. In the second case, the Xq28 breakpoint lies within the adjacent gene c6.1B, and c6.1A is not transcribed. We show that the c6.1B gene is transcribed in both of our patients. c6.1B may be important in the initial clonal proliferation of T lymphocytes which commonly precedes transformation to T-PLL in ataxia telangiectasia patients. The same gene may also be involved in the development of T-PLL in the non-A-T population.
Leukemia 1994 Apr
PMID:A gene on chromosome Xq28 associated with T-cell prolymphocytic leukemia in two patients with ataxia telangiectasia. 815 52

Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb region within the MLL gene is consistently involved, whereas in the latter breakpoints appear to be heterogeneous. In a B cell acute leukemia cell line with t(14;18)(q32.3;q21.3) we have previously demonstrated a reciprocal translocation between the LAZ3/BCL6 gene at 3q27 and the B cell specific transcriptional coactivator gene BOB-1 at 11q23.1, implicating BOB-1 as a potential proto-oncogene. To confirm the chromosomal localization of BOB-1 we have mapped it by FISH to 11q23.1. It lay immediately telomeric of the ATM gene. We have also investigated the frequency of BOB-1 rearrangements in a panel of 32 cell lines and 71 patient samples. In one case of T cell prolymphocytic leukemia-a disease where 11q23 abnormalities are observed-a chromosomal rearrangement was identified 3.3-0.9 kb centromeric of the 3' end of the gene. Thus, there is a heterogeneity of breakpoints associated with BOB-1 while the frequency of the gene's involvement in lymphoproliferative diseases is low.
Leukemia 1996 Sep
PMID:Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in lymphoproliferative disease. 875 68

B cell chronic lymphocytic leukaemia (CLL) shows evidence of familial aggregation, but the inherited basis is poorly understood. Mutations in the ATM gene have been demonstrated in CLL. This, coupled with a possibly increased risk of leukaemia in relatives of patients with Ataxia Telangiectasia, led us to question whether the ATM gene is involved in familial cases of CLL. To examine this proposition we typed five markers on chromosome 11q in 24 CLL families. No evidence for linkage between CLL and ATM in the 24 families studied and the best estimates of the proportion of sibling pairs that share no, one or both haplotypes at ATM were not different from their null expectations. This would imply that ATM is unlikely to make a significant contribution to the three-fold increase in risk of CLL seen in relatives of patients.
Leukemia 1999 Oct
PMID:Linkage analysis for ATM in familial B cell chronic lymphocytic leukaemia. 1051 48


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