1/23. TCL-1, MTCP-1 and TML-1 gene expression profile in non-leukemic clonal proliferations associated with ataxia-telangiectasia.We analyzed the role of 4 genes, TCL-1, MTCP-1, TML-1 and ATM, in the early pathogenesis of T cell leukemia, with particular interest in the characteristics of long-standing non-leukemic clonal proliferations in ataxia-telangiectasia (A-T) patients. Five patients were studied: 4 patients had A-T (2 of whom had non-leukemic clonal proliferations [ATCP]), 1 had B cell lymphoma and 1 had T-ALL; a fifth patient with T-PLL did not have A-T. We measured the levels of expression for TCL-1, MTCP-1 and TML-1. TCL-1, not expressed in unstimulated mature T cells, was upregulated in the peripheral blood leukocytes (PBL) of the 2 A-T patients with ATCP. It was also expressed in the malignant cells of the A-T patient with B cell lymphoma and the T-PLL cells of the patient without A-T. In the same cells, MTCP-1 type A was expressed equally in all 5 patients, as well as in the controls; MTCP-1 type B transcripts were not observed. TML-1, also not expressed in unstimulated T cells, was expressed in the PBL of one A-T patient with ATCP and in the leukemic cells of the non-A-T T-PLL patient. These expression patterns were compared to cellular immunophenotypes. The non-leukemic clonal T cell populations had the characteristics of immature T cells. We conclude that TCL-1 and TML-1 play a role in cell proliferation and survival but are not pivotal genes in the progression to malignancy, even when the ATM gene is mutated. Additional genetic alterations must occur to initiate tumorigenesis.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
2/23. A subtle t(3;8) results in plausible juxtaposition of MYC and BCL6 in a child with burkitt lymphoma/leukemia and ataxia-telangiectasia.Translocations involving 3q27 that affect the BCL6 gene are common and specific chromosomal abnormalities in B-cell precursor non-Hodgkin lymphoma (mainly diffuse large-cell and follicular lymphoma), but they have not been reported in burkitt lymphoma. Here, we describe a case in which a BCL6 rearrangement and additional complex cytogenetic abnormalities occurred in a child with burkitt lymphoma/leukemia and ataxia-telangiectasia. Although cytogenetic analysis of the bone marrow revealed clonal abnormalities of chromosome arms 8q and 14p and other subclonal abnormalities, the t(8;14) or its variants typically associated with burkitt lymphoma were not observed. fluorescence in situ hybridization with locus-specific probes and multicolor spectral karyotyping demonstrated a complex pattern of chromosomal rearrangements leading to a subtle t(3;8)(q27;q24.1) that rearranged BCL6 and placed it adjacent to MYC. We speculate that this genetic lesion occurred as a result of chromosomal instability due to the underlying disease.- - - - - - - - - - ranking = 5keywords = leukemia (Clic here for more details about this article) |
3/23. Ataxia-telangiectasia complicated by craniopharyngioma--a new observation.Ataxia-telangiectasia is a rare autosomal recessive neurodegenerative disorder with high incidence of malignancy including leukemias, lymphomas, and solid tumors. central nervous system tumors in ataxia telangiectasia include medulloblastomas and gliomas. We describe a 13-year-old girl with ataxia telangiectasia who developed craniopharyngioma and non-Hodgkin's lymphoma. To our knowledge, this is the first case of ataxia telangiectasia complicated by craniopharyngioma in the English literature.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
4/23. Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia.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.- - - - - - - - - - ranking = 5keywords = leukemia (Clic here for more details about this article) |
5/23. Molecular analysis of a t(14;14) translocation in leukemic T-cells of an ataxia telangiectasia patient.We have detected and cloned two rearrangements in the T-cell receptor alpha locus from a clone of somatic cell hybrids carrying a t(14;14)(q11;q32) chromosomal translocation derived from an ataxia telangiectasia patient with T-cell chronic lymphocytic leukemia. The T-cell clone carrying the t(14;14) chromosomal translocation was known to be present for greater than 10 years before the onset of overt leukemia. One molecular rearrangement of the T-cell receptor alpha locus corresponded to a functional variable-joining region (V-J) joining, whereas the other derived from the breakpoint of the t(14;14)(q11;q32) translocation. Chromosomal in situ hybridization of the probe derived from the t(14;14) breakpoint localized the breakpoint region to 14q32.1, apparently the same region that is involved in another ataxia telangiectasia characteristic chromosome translocation, t(7;14)(q35;q32). The 14q32.1 breakpoint is at least 10,000 kilobase pairs (kbp) centromeric to the immunoglobulin heavy chain locus. sequence analysis of the breakpoint indicates the involvement of a J alpha sequence during the translocation. Comigration of high-molecular weight dna fragments involved with t(7;14) and t(14;14) translocations suggests the presence of a cluster of breakpoints in the 14q32.1 region, the site of a putative oncogene, TCL1.- - - - - - - - - - ranking = 2keywords = leukemia (Clic here for more details about this article) |
6/23. Uterine tumors in ataxia-telangiectasia.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.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
7/23. Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia.A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3 T4- T6- T8 T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3 T4 T6- T8 T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11 ). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin a (ConA), stimulation of the T3-Ti receptor complex with sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.- - - - - - - - - - ranking = 7keywords = leukemia (Clic here for more details about this article) |
8/23. Helper and suppressor t-lymphocyte leukemia in ataxia telangiectasia.We investigated the nature of the lymphoid leukemia that developed in one of two siblings with ataxia telangiectasia. The leukemic cells were shown to be T lymphocytes. Furthermore, the neoplastic cells carried a characteristic 14q chromosome tandem translocation. This chromosome abnormality had been identified 11 years earlier among the patient's "normal" lymphocytes. The patient's neoplastic T lymphocytes in vitro provided helper and suppressor T-lymphocyte activity equivalent to that of normal T lymphocytes. Some neoplastic T lymphocytes bore a receptor for the Fc portion of IgM (45 per cent Tmu) whereas other carried receptors for the Fc portion of IgG (10 per cent Tgamma). All the Tmu and Tgamma lymphocytes possessed the chromosome 14 abnormality. These data suggest that neoplastic transformation occurred in an uncommitted T lymphocyte that was capable of further differentiation into the distinct pathways for help and suppression, in a lymphoid analogy of chronic myelogenous leukemia.- - - - - - - - - - ranking = 6keywords = leukemia (Clic here for more details about this article) |
9/23. The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis.T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32--the same bands in which the T-cell receptor (TCR) alpha-chain and immunoglobulin heavy chain genes have been mapped, respectively. patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. We now describe dna rearrangements of the TCR alpha-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR alpha-chain variable (V alpha) and joining (J alpha) gene segments. The other allele of the TCR alpha-chain gene features a dna rearrangement, about 50 kilobases from the TCR alpha-chain constant (C alpha) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J alpha segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C mu. These results imply that 14q32 sequences located at an undetermined distance downstream of the immunoglobulin C mu locus can contribute to the development of T-cell tumors.- - - - - - - - - - ranking = 6keywords = leukemia (Clic here for more details about this article) |
10/23. Distinct chromosome abnormalities in ataxia telangiectasia with chronic T-cell lymphocytic leukemia.We report chromosomal studies of a 27-year-old male patient with ataxia telangiectasia who developed a chronic T-cell lymphocytic leukemia. The leukemic cells grew spontaneously although a better yield of metaphases could be obtained after PHA stimulation. Chromosome analysis revealed a hypodiploid leukemic clone (44 chromosomes) and a single remaining normal metaphase. An isochromosome 8q was detected in a subclone at an early analysis, which was lost during clonal evolution. At the time of the last analysis, 6 months before the patient died, the diploid metaphases disappeared completely. The karyotype of the final chromosome study showed a monoclonal condition with the following abnormalities: 44,X,-Y,4q-,6p-,14q-,19p ,20q ,-20,22q-. Loss of the y chromosome was limited to the leukemic cells. Comparing our data with the chromosome abnormalities reported in the literature, breakpoints at band 14q11-12 (location of the gene for the alpha chain of the T-cell receptor), loss of a normal chromosome #20, as well as structural abnormalities of the remaining chromosome 20p seem to be nonrandom in T-CLL arising in patients with ataxia telangiectasia. A philadelphia-like marker that seems to be a peculiar feature of the case described here, however, resembles a small marker chromosome qualified as unidentifiable in a similar case of T-CLL reported in the literature.- - - - - - - - - - ranking = 5keywords = leukemia (Clic here for more details about this article) |
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