Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A long-term T-cell line, termed SP+, was developed from a human T-cell leukemia virus type I (HTLV-I)-infected patient with adult T-cell leukemia that is dependent on exogenous IL-2 for growth. The SP+ expresses a full complimentation of HTLV-I-specific viral proteins, and contains replication competent viral particles. Restriction enzyme digestion followed by Southern blot analysis demonstrated the presence of a single integrated proviral copy and limiting dilution analysis confirmed the clonality of the cell line. Interestingly, phenotypically, the SP+ cell line is CD2+, CD3+ and coexpresses CD4 and CD8, yet lacks TCR alpha beta and TCR tau delta expression. Further ontogenetic characterization of the SP+ cell line demonstrated the lack of thymic T-cell precursor markers, including absence of cell surface expression of CD1, intracellular thymic terminal deoxynucleotidyl transferase (TdT) enzyme, as well as message expression for V(D)J recombinase activating gene-1 (RAG-1). Furthermore, the SP+ cell did express the message for the CD3 delta chain. Taken together, these data suggest that the SP+ cell line resulted from HTLV-I infection of a mature CD4+/CDB+ lymphocyte. This cell line can be potentially useful as a model, both for regulation of cellular functions by HTLV-I and for immunologic functions of mature dual CD4/CD8 positive T-cells.
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PMID:Characterization of a HTLV-I-infected cell line derived from a patient with adult T-cell leukemia with stable co-expression of CD4 and CD8. 756 72

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.
Leukemia 1995 Oct
PMID:Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements. 756 13

The follow up of minimal residual disease (MRD) in childhood B-precursor ALL by polymerase chain reaction (PCR) may be of help for further stratification of treatment protocols, to improve outcome. However, the clinical relevance of this approach has yet to be defined. We report the retrospective follow-up of MRD in bone marrow (BM) samples from 50 childhood B-precursor ALL patients by IgH/TCR delta PCR. Twenty-two patients remained in continuous complete remission (median follow-up 61 months), and 28 experienced relapse (median follow-up 75 months). Initial regression of MRD on therapy correlated with outcome. At the end of induction therapy 2/18 (11.1%) patients from the CCR group were PCR positive vs 10/16 (62.5%) from the 'relapse' group (P = 0.005). The presence of PCR detectable MRD predicted event-free survival independent of standard clinical and cytogenetical parameters. Also subsequent to first BM relapse, a correlation between MRD regression and outcome was observed. Six of eight patients who became PCR negative in the time period between relapse and bone marrow transplantation are in CCR, whereas 7/7 patients who remained PCR positive in this time period died (P = 0.006). In approximately 70% of evaluable patients, clinical relapse was preceded by recurrence of detectable MRD at time intervals of 3-18 months earlier and the recurrence of PCR positivity after a period of negativity was always followed by overt relapse. At relapse, the combined use of IgH and TCR delta probes reduced false negativity caused by clonal evolution to approximately 10%. This study shows that the evolution of PCR detectable MRD is an independent predictor of outcome.
Leukemia 1995 Oct
PMID:Prolonged persistence of PCR-detectable minimal residual disease after diagnosis or first relapse predicts poor outcome in childhood B-precursor acute lymphoblastic leukemia. 756 17

The Ikaros gene is essential for lymphoid lineage specification. As previously reported, mice homozygous for a mutation in the Ikaros DNA-binding domain fail to generate mature lymphocytes as well as their earliest described progenitors. In addition, our studies with mice heterozygous for this mutation establish the Ikaros gene as an essential regulator of T cell proliferation. Thymocytes display augmented TCR-mediated proliferative responses, and peripheral T cells are autoproliferative. A general lymphoproliferation precedes the T cell leukemia and lymphoma that rapidly develop in all heterozygotes. The first step toward leukemic transformation occurs within the maturing thymocyte population and is demarcated by clonal expansions and loss of the single Ikaros wild-type allele. From these studies, we propose that within developing and mature T lymphocytes, distinct thresholds of Ikaros activity are required to regulate proliferation. A decrease in Ikaros activity below the first threshold causes the rapid accumulation of T lymphoblasts, whereas a further decrease leads to neoplastic transformation.
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PMID:A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. 758 46

Murine AIDS (MAIDS) is induced by infection with the replication-defective virus (BM5def) component in the LP-BM5 murine leukemia virus (MuLV) mixture. The disease is characterized by polyclonally activated CD4+ T cells and B cells. It is known that BM5def is expressed at highest levels in B lymphocytes and that B cells serve as viral antigen-presenting cells. Full and sustained activation of CD4+ T cells against a conventional Ag usually requires both TCR and costimulating signals. Among various molecules known to provide costimulatory function, the expression of CD54 (ICAM-1) and CD11a/CD18 (LFA-1) on MAIDS B cells was increased, whereas that of CD2, heat-stable Ag (CD24), CD80 (B7-1), and CD86 (B7-2) was unchanged from normal. C57BL/6 mice depleted of both CD54 and CD11a expression as a result of chronic administration of mAb had developed no MAIDS at 4 wk and 8 wk after LP-BM5 MuLV infection. In addition, the proliferative response of B cells to mitogen was well conserved, whereas MAIDS-associated increases in serum Ig levels were inhibited. Replication of BM5def was suppressed markedly in infected mice treated with the CD54 and CD11a mAbs. These results suggest that the CD54/CD11a signal transduction pathway is a critical determinant of MAIDS development, and the lack of an immune response against viral Ag is enough to suppress BM5def replication and to prevent MAIDS.
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PMID:Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a. 760 73

The Moloney murine leukemia virus (Mo-MLV) enhancer contains binding sites (LVb and LVc) for the ets gene family of proteins and a core site that binds the polyomavirus enhancer-binding protein 2/core-binding factor (cbf) family of proteins. The LVb and core sites in the Mo-MLV enhancer contribute to its constitutive activity in T cells. All three binding sites (LVb, LVc, and core) are required for phorbol ester inducibility of the Mo-MLV enhancer. Adjacent binding sites for the ets and cbf proteins likewise constitute a phorbol ester response element within the human T-cell receptor beta-chain (TCR beta) enhancer and contribute to constitutive transcriptional activity of the TCR beta enhancer in T cells. Here we show that the CBF alpha subunit encoded by the mouse Cbfa2 gene (the murine homolog of human AML1) and three ets proteins, Ets-1, Ets-2, and GA-binding protein (GABP), transactivate both the Mo-MLV and mouse TCR beta enhancer in transient-expression assays. Moreover, we show that transactivation by Cbf alpha 2 requires both intact ets and cbf binding sites. Transactivation by Ets-1, Ets-2, and GABP likewise requires intact binding sites for ets proteins and CBF. Supportive biochemical analyses demonstrate that both proteins can bind simultaneously to a composite enhancer element. These findings suggest that ets and cbf proteins cooperate in vivo to regulate transcription from the Mo-MLV and TCR beta enhancers.
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PMID:Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins. 760 63

Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we reported that autoantibodies were elevated during the initiation phases of this murine retrovirus infection and bound peptide determinants corresponding to CDR1 of several TCR V beta-chains. Therefore, we designed studies to determine whether administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation of T cell function. Administration of the TCR V beta CDR1 peptide before murine retrovirus infection significantly prevented its suppression of splenic NK cell activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk postinfection. However, delaying peptide immunization until severe suppression of T and B cell mitogenesis had occurred did not restore their functions. Immunization with TCR V beta peptide prevents development of retrovirus-induced immune dysfunction, which suggests a possible pathogenic role of autoreactive T cells as regulatory elements.
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PMID:T cell receptor V beta complementarity-determining region 1 peptide administration moderates immune dysfunction and cytokine dysregulation induced by murine retrovirus infection. 763 74

We present a case of granular lymphocytic leukemia (GLL) associated with pure red cell aplasia (PRCA). Twenty-seven percent of the peripheral blood mononuclear cells (PBMC) were positive for TCR delta 1, but not for delta TCS1 (V delta 2), and a rearrangement of the TCR chain (J delta 1) gene was detected. The PBMC and serum from the patient slightly suppressed CFU-E but not BFU-E colony formation in vitro. These findings suggest that monoclonal proliferation of TCR gamma delta-positive granular lymphocytes (GL) can be associated with PRCA even in a patient having a small proportion of leukemia GL, which we propose to designate as 'smoldering GLL'.
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PMID:Smoldering gamma delta T-cell granular lymphocytic leukemia associated with pure red cell aplasia. 765 9

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

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.
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PMID:Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia. 767 5


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