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

The presence of human T-cell leukemia virus (HTLV-1) in patients with adult T-cell leukemia (ATL) was investigated by Southern blotting and in situ hybridization. In all seven patients, HTLV-1 provirus was detected. A large and variable number of labeled restriction fragments were observed, indicating multiple integrations. Two of the patients analyzed by in situ hybridization had two, while the third patient had three, sites of viral integration on six different chromosomes, suggesting random integration. A single site of integration was shared by two patients, which was on chromosome 10 at bands p11-->p15. One of these sites was on an apparently normal chromosome 10 and the other was on a derivative chromosome 10,t(10;14)(p12;q32). The interleukin 2 receptor (IL2R) has previously been localized to this region (10p14-->p15). The alpha-chain of the IL2R is continuously expressed on affected T-cells in this disease. Southern blotting with pIL2R showed the presence of a novel 3.5 kb fragment in five out of the seven patients. This novel fragment has not been previously reported. No direct correlation was found between the novel 3.5 kb fragment, present in patients both cytogenetically normal and abnormal, and viral integration in the 10p11-->p15 region in two patients. Therefore, it is suggested that the presence of the 3.5 kb fragment and the numerous chromosomal breaks associated with this disease may not be direct results of viral integration.
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PMID:Chromosomal localization of HTLV-1 viral integration sites using in situ hybridization: detection of a novel IL2R fragment. 135 40

Acute myeloid leukaemia (AML) blast cells express haemopoietic growth factor receptors. However, their presence does not predict response to the cognate ligand in vitro. This suggests that haemopoietic growth factor receptor structure or function may be abnormal in some cases of acute myeloid leukaemia. The granulocyte-macrophage colony-stimulating factor receptor alpha-chain gene (GM-CSF-R) has recently been localised to the pseudoautosomal region of the sex chromosomes. A sex chromosome is lost in 25% of cases of AML FAB subtype M2. The loss of one allele of this gene may have some aetiological significance in AML if the other allele is altered leading to abnormal receptor structure, function or number. In this initial study, we have examined DNA from leukaemic cells of 29 patients with AML, including three with FAB subtype M2 with deletion of an X or Y chromosome for evidence of gross rearrangement of this gene. We report that although the gene is highly polymorphic for a number of restriction enzymes, we have found no evidence of gross rearrangement in AML.
Leukemia 1992 Sep
PMID:Human GM-CSF receptor alpha-chain gene is highly polymorphic but not rearranged in AML. 138 92

We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2R alpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2R alpha at 24 h after induction by IL-6 is strongly enhanced by IL-1. However, IL-1 does not change the transient kinetics of expression of IL-2R alpha. Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1. By Northern analysis, we find that the increase in IL-2R alpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2R alpha but not IL-2R beta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2R alpha mRNA expression is due to both an increase in IL-2R alpha gene transcription and to an increase in IL-2R alpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2R alpha can be specifically up-regulated by IL-1, however, without affecting the transient nature in expression of IL-2R alpha.
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PMID:Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism. 142

The Tax1 protein of human T cell leukemia/lymphoma virus type I (HTLV-I) has been shown to stimulate the proliferation of human lymphocytes. Here we report that lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha-chain (IL-2R alpha) expression in human lymphocytes. Functional activation of IL-2R alpha expression in peripheral blood lymphocytes treated with Tax1 was demonstrated using an [125I]IL-2-binding assay. In addition, an enzyme-linked immunosorbent assay demonstrated that soluble IL-2R alpha in the medium of IL-2- and Tax1-treated cells was over 13-fold greater than in the medium of control treated cells. Overexpression of IL-2R alpha is a common clinical feature of some patients with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myopathy (TSP/HAM). The ability of extracellular Tax1 protein to activate expression of IL-2R alpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed in both ATL and TSP/HAM.
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PMID:Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis. 150 87

Soluble suppressor factor (SSF), first described in association with HIV-1 infection in vivo, is a molecule(s) capable of inhibiting T cell-dependent immune reactivity. Its relationship to human immunodeficiency virus (HIV) was further defined as supernatants of mononuclear cell cultures from HIV-1-seropositive carriers, CD4+ T lymphocytes infected with HIV-1 in vitro, and a T cell hybridoma incorporating CD4+ lymphocytes from an HIV-1-seropositive individual were shown to elaborate factors with similar activity profiles. These factors were recognized antigenically by certain antibodies directed against epitopes of p15E, a transmembrane protein of murine leukemia virus which shares regions of identity with proteins deduced from human endogenous retroviral envelope transcripts as well as HIV. These reagents precipitated a single-chain, nonglycosylated, nonviral protein of molecular weight 57,000 Da from SSF-producing cells. There was no cross-reactivity with antisera recognizing the IL-2R alpha-chain (CD25) or tumor necrosis factor. This molecule was present in very low levels in PHA-activated T lymphocytes and was upregulated following their infection with HIV-1. Isolation of HIV-linked SSF should permit comparisons with other virion, cellular, and serum inhibitory substances described in AIDS, and perhaps suggest therapeutic strategies.
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PMID:A soluble inhibitor of T lymphocyte function induced by HIV-1 infection of CD4+ T cells: characterization of a cellular protein and its relationship to p15E. 169 8

The close association between adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) has been established. Nevertheless, the mechanism of progression of ATL by HTLV-I infection is still uncertain, because the virus contains no typical oncogene and no significant expression of the viral RNA has been generally found. I propose a model of leukemogenic process in ATL based on our cytogenetic data and molecular results in the literature. It seems that the rearrangement of some proto-oncogene and alpha-chain gene of the T-cell antigen receptor (TCR-alpha) is necessary for the development to overt ATL. A deficiency in the rearrangement of proto-oncogene to TCR-alpha may result in only a minor proliferation of abnormal lymphocytes and remain in the preleukemic state of ATL or in the HTLV-I carrier state.
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PMID:Cytogenetic implication in adult T-cell leukemia. A hypothesis of leukemogenesis. 198 42

The kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor.
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PMID:Comparison of constitutive and inducible transcriptional enhancement mediated by kappa B-related sequences: modulation of activity in B cells by human T-cell leukemia virus type I tax gene. 200 51

A 13-year-old girl with acute lymphoblastic leukemia is presented. The peripheral smear showed, in addition to lymphoblasts, marked anisocytosis, poikilocytosis, and polychromasia. In vitro sickling test was positive. Hemoglobin electrophoresis at pH 9.0 on starch gel revealed the presence of hemoglobin A, hemoglobin S, and a band with a mobility of hemoglobin A2. Structural analysis revealed the presence of hemoglobin S and an alpha-chain variant, hemoglobin Q-Iran. The patient attained remission with the initial therapy administered but a relapse occurred five months later. Our study indicates the need for detailed investigation of leukemia patients in which abnormal hemoglobins are prevalent.
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PMID:Acute lymphoblastic leukemia in a child with hemoglobins S and Q-Iran. 228 17

High-affinity receptors for interleukin 2 (IL-2) are expressed on T cells following activation. These receptors are composed of both alpha and beta chains. Expression of alpha chains and, therefore, expression of high-affinity receptors are critically regulated at the level of transcription initiation. We have further dissected the regulatory elements involved in controlling transcription of the IL-2 receptor alpha-chain (IL-2R alpha) gene. The IL-2R alpha promoter contains a kappa B site and binding sites for additional nuclear factors within a 50-base-pair region (positions -290 to -240 relative to the major transcription start site). These include one upstream of the kappa B site and one similar to the c-fos serum response element (SRE), which is downstream of the kappa B site. Mutation of the kappa B site decreases IL-2R alpha promoter activity in MT-2 cells (a T-cell line that has been transformed with human T-cell lymphotropic virus type I), but not in Jurkat cells (a T-cell leukemia line) that have been activated by phorbol 12-myristate 13-acetate (PMA). In contrast, mutation of a region upstream of the kappa B site decreases activity in PMA-induced Jurkat cells but increases activity in MT-2 cells. Mutation of the SRE-like site decreases activity in both cell types but the effect in PMA-induced Jurkat is more pronounced. Thus, these distinct cis-acting elements play different physiological roles in IL-2R alpha gene activation in MT-2 cells and PMA-induced Jurkat T cells. These studies provide direct evidence for a functionally significant SRE-like sequence in a gene other than c-fos and the actin genes and identify other elements that are critical for IL-2R alpha gene expression.
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PMID:The same target sequences are differentially important for activation of the interleukin 2 receptor alpha-chain gene in two distinct T-cell lines. 230 42

The expression of the gene encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1, a transactivating protein of the human T-cell leukemia virus type I. The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes, depending on promoter elements that bind the inducible transcription factor NF-kappa B (or an NF-kappa B-like factor). We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor. A recent functional analysis by Miyatake et al. (S. Miyatake, M. Seiki, M. Yoshida, and K. Arai, Mol. Cell. Biol. 8:5581-5587, 1988) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1, but no NF-kappa B-binding motifs were identified. Using electrophoretic mobility shift assays, we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1. As shown by a methylation interference analysis and oligonucleotide competition experiments, purified NF-kappa B binds at positions -82 to -91 (GGGAACTACC) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter (GGGAAATTCC). Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities. Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter.
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PMID:NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene. 240 68


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