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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have sought to address the question of clonal variation of TCR within a human T leukemia cell line, HPB-ALL. To do so, a panel of anti-idiotypic antibodies was produced and the cell line examined for variants. We isolated both spontaneous idiotype and receptor-negative variants without applying mutagens or any selective pressure other than sorting the cells. These sorted and cloned populations are all clonally related to each other as shown by their beta-TCR locus gene rearrangements. The idiotype variants have alpha-chains which are differentially glycosylated, but they have the same size core protein after treatment with peptide N-glycosidase F to remove their carbohydrate side chains. This probably accounts for their idiotypic difference, since the antibody that distinguishes them appears dependent upon glycosylation for its binding, as shown by immunoprecipitation in the presence versus the absence of tunicamycin, which inhibits glycosylation from occurring. The idiotype variants differed from one another in variable region sequences by only a single amino acid substitution in the beta-chain, which is likely not important for the idiotypic difference. The receptor-negative variant produces both alpha- and beta-mRNA and cytoplasmic protein for TCR, but fails to transport this protein to the cell surface. We conclude that idiotype and receptor-negative variants of a T cell clone can occur in the absence of appreciable somatic mutation.
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PMID:Spontaneous T cell antigen receptor variants of a human T leukemia cell line. 326 74

The use of probes to genes (IG and TCRB) encoding immunoglobulins (IG) and the beta chain of the T-cell antigen receptor (TCRB), respectively, have become a sensitive means to assess clonality and lineage in lymphoid malignancies. It has become apparent that some individual cases show rearrangements of both IG and TCRB genes. In an attempt to more accurately define cell lineage we have analyzed cells from patients with B- or T-cell leukemia (n = 26) at various stages of maturation with probes to two additional TCR genes, TCRG and TCRA (encoding the TCR gamma and alpha chains, respectively), as well as the IG heavy chain joining region (IGHJ) and TCRB genes. On Southern blot analysis, the mature T-cell leukemia cells studied had rearranged TCRG and TCRB while IGHJ remained as in the germ line. The mature B-cell leukemia cells studied had rearranged IGHJ with germ-line TCRG and TCRB. These data suggest that, in the majority of more mature leukemias, cells have rearranged IG or TCR genes but not both. In contrast, cells from five of nine precursor B-cell leukemia patients and cell lines from one of four precursor T-cell leukemia patients had rearranged both IGHJ and TCR genes. TCRG and TCRB mRNAs were expressed in the cells of precursor T- but not B-cell leukemia patients studied. The spectrum of leukemia cells studied within the T-cell series permitted an assessment of the order of TCR gene rearrangements. Two of 13 patients had cells with germ-line TCRG and TCRB, 2 patients had cells with rearranged TCRG alone, and the remainder had cells with rearranged TCRG and TCRB. TCRG and TCRB mRNAs were expressed in precursor T-cell leukemia cells, whereas TCRB and TCRA were expressed in mature T-cell leukemia cells. These results parallel observations from mouse studies on gene expression and support the view of a hierarchy of TCR gene rearrangements in T-lymphocyte ontogeny. TCRG genes are rearranged first, subsequently TCRB genes are rearranged, followed by TCRA gene activation.
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PMID:Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. 346 80

Instability of antigen receptor gene rearrangements during progression of acute lymphoblastic leukemia (ALL) has important implications for polymerase chain reaction (PCR)-based techniques using these genes for the detection of minimal residual disease (MRD). Antigen receptor gene instability may lead to false negative results in bone marrow samples taken during remission. Utilizing the PCR and consensus primers for rearranged immunoglobulin heavy chain (IgH) and T cell receptor gamma (TCR gamma) gene sequences, we analyzed the bone marrow samples at diagnosis and first relapse for 37 children with ALL. The incidence of clonal evolution at the IgH locus was 9/33 (27%) and at the TCR gamma locus 1/15 (7%). In four of the nine patients with clonal evolution at the IgH locus, the sequence at relapse retained the diversity and joining region (D-N-J) sequences from diagnosis. Patients with clonal evolution were characterized by a higher incidence of more than one IgH PCR band at diagnosis and by late relapse (> 18 months from diagnosis). These results suggest that, where possible, patients with more than one IgH PCR rearrangement at diagnosis should be monitored using another antigen receptor gene, such as TCR gamma, since evolution for this gene was found to be a rare event. By combining this approach with a strategy directed at the more stable D-N-J region of the IgH gene, MRD false negativity would have occurred in less than 10% of patients in the present study.
Leukemia 1995 Nov
PMID:Characterization of clonal immunoglobulin heavy chain and I cell receptor gamma gene rearrangements during progression of childhood acute lymphoblastic leukemia. 747 73

We established a novel T cell line, designated TK-6, from a patient with T cell lineage blast crisis of chronic myelogenous leukemia (CML) complicated by hypercalcemia. A surface marker study showed T cell phenotype, cluster designation (CD)4, CD5 and CD7. Light and electron microscopic examination revealed myeloperoxidase (MPO)-negative, however, ultrastructural examination under certain specific conditions demonstrated that some cells were MPO-positive. The TK-6 cell karyotype carried a t(9;22)(q34;q11) and additional chromosome aberrations, including a deletion of the long arm of chromosome 6 and the abnormality of chromosome 7. Southern blot analysis showed rearrangement of the T cell receptor beta-chain (TCR beta) gene and the major breakpoint cluster region (bcr) gene. Northern blot analysis detected the expression of the parathyroid hormone-related protein (PTHrP) gene, however, the proviral genome of human T cell leukemia virus type I (HTLV-I) was negative. This cell line will provide a valuable resource for the analysis of the relationship between T cell lineage crisis and myeloid differentiation and for the analysis of humoral hypercalcemia of malignancy (HHM) or leukemia.
Leukemia 1995 Nov
PMID:Establishment and characterization of a novel cell line, TK-6, derived from T cell blast crisis of chronic myelogenous leukemia, with the secretion of parathyroid hormone-related protein. 747 85

This article discusses the most important information on health effects in the Urals region (Russia) of residents exposed to radiation from activities of a weapon plutonium separation plant. The population residing on the contaminated territory was exposed to chronic combined irradiation (external gamma-irradiation and internal irradiation due to Sr-90 and Cs-137). The red bone marrow (RBM) was the critical organ affected as a result of radiation events in the Urals. In the early period, after the discharges of radioactive wastes into the river Techa (about 3 M Ci) started, cases of chronic radiation sickness (CRS; 940 cases, in total), postirradiation reactions manifested by changes in blood parameters (e.g., leukopenia, thrombocytopenia, granulocytopenia), nervous system disorders, immunity changes and ostealgic syndrome were registered in a portion of those riverside village residents who had received the highest doses. Increased leukemia and cancer mortality and morbidity rates were noted among this population in later periods. No late effects were observed in residents exposed to an explosion in a radioactive waste depot in September, 1957 when radioactive wastes with about 20 M Ci of activity were released into the environment. Similarly, the offspring of the residents exposed on the Techa also did not display any late effects. The data about the possibilities of long-term (43-45 years after the start of exposure) biological indication of chronic internal exposure are presented. The methods used in the study include in situ fluorescent hybridization, analysis of mutations in the TCR gene of peripheral blood lymphocytes and erythrocyte mutations in the glycophorine A system. No dependence of genomic translocations and mutations in glycophorine A on cumulative exposure dose to RBM was traced.
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PMID:Health effects of radiation incidents in the southern Urals. 748 69

It has been established that, even after syngeneic bone marrow transplantation, animals treated with immunosuppressive drugs may suffer from graft-versus-host disease, showing autoimmune-like symptoms. Although the major effector cells are known to be T-cell subsets, detailed characterization of such T cells remains to be investigated. In the present study, we characterized them, especially as to whether they are thymus-derived T cells or extrathymic T cells, and how self-reactive clones were distributed among the above T-cell subsets. BALB/c mice (Mls-1b2a) were irradiated (9 Gy), subjected to bone marrow transplantation, and then treated with cyclosporin A (CsA) for 6 weeks. From 2 weeks after the cessation of CsA, these mice displayed signs of GVH disease. The major target organs included the liver and colon. Two-color staining for CD3 and IL-2R beta was applied to identify CD3-IL-2R beta+ NK cells, CD3-intermediate +IL-2R beta+ cells (i.e., intermediate CD3 or TCR cells of extrathymic origin) and CD3-high+IL-2R beta- cells (i.e., high CD3 cells of thymic origin). It was demonstrated that the major expanding lymphocytes were intermediate TCR cells and that self-reactive clones (V beta 3+ and V beta 11+ cells in this strain of mice) were confined to this population. Interestingly, these self-reactive clones had ability to respond to immobilized anti-V beta 3 and anti-V beta 11 mAbs. Liver MNC in mice with GVH disease which contained the highest proportion of intermediate TCR cells were able to mediate the adoptive transfer of GVH disease to other irradiated (6.5 Gy) mice. Intermediate TCR cells also showed potent cytotoxic activity against syngeneic leukemia cells. These results suggest that intermediate TCR cells are the major effector cells for the induction of syngeneic GVH disease.
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PMID:Intermediate TCR cells with self-reactive clones are effector cells which induce syngeneic graft-versus-host disease in mice. 749 19

Recent studies of the TCR alpha and beta chains expressed by normal human IELs suggest that these intestinal lymphocytes are directed at a limited set of antigens, presumably on intestinal epithelial cells in view of their anatomic location. The direct sequence analysis of these cells has indicated that they are oligoclonal and cannot, therefore, be responding to the complex mixture of antigens which are present in the lumen. The abundant expression of the CD8 accessory molecule by the IELs, in addition, indicates that these putative intestinal epithelial cell antigens are presented by MHC class I or I-like molecules. The expression of CD8 also suggests that these cells function biologically in part as cytolytic T lymphocytes which is consistent with a variety of functional studies. Taken together with their expression of the CD45RO isoform, these phenotypic and functional observations suggest that iIELs are cytolytic, memory cells which are responsive to an extremely limited number of antigens bound to major histocompatibility complex (MHC) class I or class I-like molecules. Several non-polymorphic MHC class I-like molecules such as Qa, the thymus leukemia antigen (TL) and CD1 in the mouse and CD1 in human represent important candidate ligands for these oligoclonal iIELs. TL and CD1 are expressed specifically by murine intestinal epithelial cells. In humans, CD1d is constitutively expressed by intestinal epithelial cells. In addition, we have isolated iIEL T cell clones which specifically recognize members of the CD1 gene family when expressed on a transfected B cell line that lacks HLA-A and B and have shown that the proliferation of peripheral blood T cells to intestinal epithelial cells is CD1d dependent. Thus, the evidence to date strongly implicate the nonpolymorphic, class Ib molecules as novel restriction elements for unique populations of lymphocytes within the intestinal epithelium.
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PMID:Intraepithelial lymphocytes and their recognition of non-classical MHC molecules. 752 51

We report here a CD7 positive undifferenciated leukemia/lymphoma which showed a rapid clinical course. A 27-year-old female was complained of palpitation and edema. She had a mediastinal tumor and pericardial effusion. Lymphoblastic cells were found in the effusion, but in the peripheral blood initially. After admission the blast cells appeared in the peripheral blood, and they were revealed negative for peroxidase and had phenotype of CD7 and CD33 positive. The patient suffered from cardiac tamponade and died 15 days after admission. The Southern blotting of mediastinal tumor cells disclosed the germline configuration for TCR-beta a chain and the rearrangement of immunoglobulin heavy chain genes.
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PMID:[CD7 positive undifferenciated leukemia/lymphoma associated with leukemic pericarditis]. 752 May 12

Several studies have suggested that activation-induced apoptosis of Ag-specific CD4+ T cells leads to depletion of this subset during HIV infection. The bacterial superantigen, staphylococcal enterotoxin A (SEA), is known to induce activation-induced apoptosis in the TCR V beta-bearing CD4+ T cells in the periphery after clonal expansion of these cells. The murine retroviral model of AIDS (MAIDS), which is induced by LP-BM5 murine leukemia virus, shares many common features with HIV infection in humans, except that CD4+ T cells increase progressively in susceptible strains. In this study, we challenged SEA to MAIDS mice and examined whether this retrovirus affects the fate of the SEA-reactive CD4+ T cells in vivo. At 4 wk post-infection with LP-BM5 murine leukemia virus, clonal expression and subsequent deletion of SEA-reactive CD4+V beta 3+ T cells occurred normally after SEA administration, whereas in vitro proliferative responses were severely impaired. At 8 wk postinfection, the in vivo expansion of CD4+V beta 3+ T cells was evident, but not followed by clonal deletion, as late as 14 days after SEA administration. This expanding subset in the infected mice expressed the Fas Ag in the same amount as the same subset in uninfected controls. These findings suggest that activation-induced apoptosis of superantigen-reactive CD4+ T cells is interfered with in vivo during the course of MAIDS, which is not attributable to underexpression of the Fas Ag by the CD4+ T cells.
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PMID:Clonal expansion but lack of subsequent clonal deletion of bacterial superantigen-reactive T cells in murine retroviral infection. 752 98

One of the earliest responses of T and B lymphocytes to stimulation through their antigen receptors is the activation of protein tyrosine kinases and the tyrosine phosphorylation of multiple cellular substrates. Here we describe a tyrosine kinase substrate, fakB, a putative homologue of the focal adhesion kinase pp125FAK. Tyrosine phosphorylation of fakB was rapidly augmented in human T and B cells following antigen receptor cross-linking with antibody, while pp125FAK was nonresponsive. Costimulation of the T-cell antigen receptor (TCR/CD3) with either the CD2 or CD4 costimulatory receptors induced synergistic fakB tyrosine phosphorylation in normal human T cells. Engagement of TCR/CD3 induced the stable association of fakB with ZAP-70, the TCR/CD3 sigma-chain-associated tyrosine kinase involved in antigen receptor-induced T-cell activation. In addition, preformed complexes of fakB and ZAP-70 were observed in T-cell leukemia lines. Phosphorylation of fakB on serine, threonine, and tyrosine residues was observed both in vivo and in vitro, where a functional increase of in vitro kinase activity was observed following TCR/CD3 stimulation. fakB is thus a focal adhesion kinase-related tyrosine kinase substrate that is differentially regulated from that of pp125FAK and likely plays a role in antigen-induced lymphocyte signaling.
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PMID:Lymphocyte antigen receptor activation of a focal adhesion kinase-related tyrosine kinase substrate. 752 94


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