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)

The envelope (env) and structural (gag) gene products of human T-cell leukemia (lymphotropic) virus type III were identified by immunoaffinity chromatography, immunoprecipitation, and two-dimensional oligopeptide mapping methods. The env gene specifies a glycosylated polypeptide with a molecular weight of 160,000 (gp160) that is processed to gp120 and smaller gene products. The gag gene specifies two polypeptides of 70,000 and 55,000 molecular weight (p70 and p55), both of which contain p24, the major structural protein of the mature virion. The techniques in this study can be used to define the extent of variability of the env gene product among different virus isolates and may identify the nature and patterns of the humoral immune response that lead to an immunologically protected state.
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PMID:Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. 298 74

Adult T-cell leukemia (ATL) is a leukemia caused by a monoclonal expansion of HTLV-I-infected T-cells expressing a CD4 antigen. The clinical features of ATL include lymphadenopathy, hepatosplenomegaly, frequent skin lesions, hypercalcemia and a rapidly fatal course. The cell surface phenotype, cytogenetics and functions of leukemic cells are described in association with various clinical manifestations and HTLV-I infection. Leukemic cells constitutively express the p55 (Tac antigen) subunit of the interleukin-2 (IL-2) receptor. Its association with the function of HTLV-I gene products and its possible role in the leukemogenesis of ATL are discussed. Finally, the potential of some therapeutic agents which may selectively eliminate the Tac-expressing leukemic cells in vitro are described, and these may provide an improvement over currently ineffective combination chemotherapy.
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PMID:Adult T-cell leukemia. 306 29

A murine Radiation leukemia virus-induced T cell lymphoma, 5C2, which is dependent on interleukin-2 (IL-2) for proliferation has been analyzed for interleukin-2 receptor (IL-2R) expression. Using fluorescence-activated cell sorter and electron microscopic analysis together with antibody specific for the known p55 chain of the murine IL-2R, no evidence has been obtained to suggest that these cells express detectable numbers of receptors with high affinity for IL-2. However, two different antibodies with specificity for the p55 chain of the IL-2R have been shown to inhibit 5C2 proliferation. An analysis of 125I-IL-2 binding has precluded a cell surface receptor density of greater than 80 molecules per cell. A temperature-dependent, nonspecific uptake of 125I-IL-2 has been described for 5C2. Uptake is saturated at 8.5 nM 125I-IL-2 with equilibrium being established within 60 min. When incubated at 37 degrees C in the presence of 400 pM 125I-IL-2, a maximum of approximately 2,000 molecules are internalized within 40 min. Uptake of other iodinated proteins by 5C2 was not observed. This property is unique to 5C2 and not to the control C6VL/1 cell line. Intracellular vesicles have also been found in 5C2 cells by electron microscopy which stain positively with gold-conjugated antibody specific for the p55 chain of the IL-2R. 5C2 appears to exhibit unique IL-2 regulatory characteristics.
Leukemia 1988 Jun
PMID:Internalization of IL-2 by an IL-2-dependent murine T cell lymphoma expressing no detectable cell surface receptors for IL-2. 313 97

The FBR murine osteosarcoma virus complex induces bone tumors with a similar latency and pathology to those induced by the FBJ virus complex. FBR murine sarcoma virus ( FBR -MSV) has been isolated from its helper virus(es) by the establishment of transformed nonproducer cells. These cells were found to express a 75,000-Da protein (P75) which was antigenically related to the p55 oncogene product of the FBJ murine osteosarcoma virus ( FBJ -MSV). P75 also contained antigenic determinants of murine leukemia virus (MLV) gag gene p15, p12, and p30 proteins, and is therefore a gag- fos fusion protein ( P75gag - fos ). P75gag - fos is a phosphoprotein and is found primarily in the nucleus. Only a single species of RNA, of 3.3 kb, was identified in FBR -MSV-transformed nonproducer cells using both fos and MLV probes, which suggested that P75gag - fos was expressed from genome-sized RNA. Chromosomal DNA from one nonproducer cell line was found to contain a single EcoRI restriction fragment of 12 kb pairs (kbp) which encompassed the FBR -MSV provirus. This DNA fragment was molecularly cloned into bacteriophage Charon 30 (lambda FBR -1), and a 7.5-kbp HindIII restriction fragment containing the entire provirus was subsequently subcloned into pBR322 ( pFBR -1). DNA from pFBR -1 was capable of inducing morphological transformation of mouse and rat fibroblasts in tissue culture. In addition, transfected cells expressed the FBR -MSV P75gag - fos protein.
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PMID:FBR murine osteosarcoma virus. I. Molecular analysis and characterization of a 75,000-Da gag-fos fusion product. 620 14

Several sarcoma-inducing viruses encode protein kinases that phosphorylate tyrosine residues. Such enzymatic activities can be detected within the detergent-insoluble matrix of transformed fibroblasts. We have analysed the protein kinase activities in two murine lymphoma cell lines ( MBL2 and LSTRA) induced by Moloney murine leukemia virus (Mo-MuLV). After incubation of the detergent-insoluble matrix of these cells with [gamma-32P]ATP, several alkali-resistant phosphoproteins, including a very heavily labelled 55 000 mol. wt. protein ( p55 ), have been detected in LSTRA, reflecting the activity of a protein kinase specific to this cell line. This protein kinase activity shares some of the distinctive properties of the protein kinases of transforming viruses, i.e., specificity for tyrosine residues, association with membranous and/or cytoskeletal structures, and inhibition by a synthetic peptide derived from the phosphorylation site of pp60src. In view of the absence of a transforming gene in MoMuLV , it is likely that the high level of protein kinase detected in the LSTRA cell line arises from the expression of a cellular gene.
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PMID:High level of tyrosine protein kinase in a murine lymphoma cell line induced by Moloney leukemia virus. 632 81

The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent for adult T-cell leukemia and tropical spastic paraparesis/HTLV-1-associated myelopathy. The HTLV-1 Tax1 gene product has been shown to transactivate transcription of viral and cellular promoters. To examine the biochemical mechanism of Tax1 transactivation, we have developed an in vitro transactivation assay in which wild-type Tax1 is able to specifically transactivate a polymerase II promoter through upstream Tax1-responsive elements. The in vitro system utilizes the HTLV-1 21-bp repeats cloned upstream of the ovalbumin promoter and G-free cassette. Purified Tax1 specifically transactivates this template 5- to 10-fold in a concentration-dependent manner. No transactivation of the ovalbumin promoter (pLovTATA) template control was observed. Tax1 transactivation was inhibited by low concentrations of alpha-amanitin and was effectively neutralized by anti-Tax1 but not control sera. Consistent with in vivo transactivating activity, Tax1 NF-kappa B mutant M22, but not cyclic AMP-responsive element-binding protein mutant M47, transactivated the template containing the tandem 21-bp repeat. In a reconstituted in vitro transcription assay, Tax1 transactivation was dependent upon basal transcription factors TFIIB, TFIIF, Pol II, TFIID, and TFIIA. TATA-binding protein did not functionally substitute for TFIID in the transactivation assay by Tax1 but was sufficient for basal transcription. Finally, we have used anti-TFIIA antibody (p55) to ask if Tax1 transactivation required TFIIA activity. Addition of TFIIA antibody to in vitro transcription reactions, as well as depletion of TFIIA by preclearing with antibody, showed that TFIIA was required for Tax1 transactivation. Only a slight (twofold) drop of basal transcription was observed. Tax1 transactivation was restored when purified HeLa TFIIA was added back into the reconstituted system. We propose that Tax1 utilizes a transactivation pathway involving the activator regulated basal transcription factors TFIID and TFIIA.
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PMID:Transactivation of the human T-cell lymphotropic virus type 1 Tax1-responsive 21-base-pair repeats requires Holo-TFIID and TFIIA. 760 77

Adult T cell leukemia-derived factor (ADF)/Thioredoxin (TRX), originally defined as an IL-2 receptor alpha-chain/p55 inducer, has many cytokine-like activities. We reported that the release of major basic protein (MBP) from mature eosinophils stimulated with cytochalasin B and C5a were augmented after preincubation with recombinant ADF/TRX. The addition of a TRX specific inhibitor, BE40644, suppressed the augmentation of MBP release from mature eosinophils. It is suggested that BE40644 is applicable in allergic diseases associated with eosinophils.
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PMID:Role of ADF/TRX and its inhibitor on the release of major basic protein from human eosinophils. 765 31

Leukemias induced with the v-abl or BCR/ABL oncogene undergo a process of tumor progression which suggests that the ABL oncogene is required but not sufficient for full transformation. In order to identify cellular changes that correlate with progression to full transformation in v-abl transformed lymphoblasts Abelson virus (A-MuLV)-infected murine bone marrow was plated over a pre-established stromal feeder layer. Shortly after A-MuLV infection, transformed lymphoblasts were poorly oncogenic, but over time, progressed in a stepwide manner to a more oncogenic state. The transformants first acquired the ability to grow efficiently in agar, but only over the feeder layer. They next progressed to efficient feeder-independent growth in liquid culture, and then to efficient feeder-independent growth in soft agar. Cell lines that reached the advanced stage of feeder-independent agar growth showed increased detection by antiphosphotyrosine Western blot of the GAP-associated p62 phosphoprotein as well as of a 55 kDa phosphoprotein while detection of the P160 v-abl phosphoprotein remained constant throughout all stages of progression. Although the identity of the p55 phosphoprotein and the mechanism by which detection of p55 and p62 phosphoproteins change on the Western blots during tumor progression are unknown, the data demonstrate that these changes strongly correlate with the stage of progression of v-abl-transformed cells and raise the possibility that these changes may play a role in tumor progression in this model.
Leukemia 1995 Jan
PMID:Increased detection of specific tyrosine phosphoproteins correlates with tumor progression of Abelson virus-infected lymphocytes. 784 13

The enhancer of Moloney murine leukemia virus (Mo-MuLV) contains an array of transcriptional control elements that direct viral gene expression in diverse cell types. The murine transcription factor Ets-1 was shown to bind to the LVb and LVc elements of the enhancer by DNase I protection and methylation interference assays. Enhancers containing disrupted Ets-1 binding sites were tested in transient expression assays in the murine T-cell line EL4.E1; alterations in the LVb element affected constitutive enhancer activity, while mutation of either the LVb or LVc element disrupted phorbol ester-induced enhancer activity. Members of the ets gene family of proteins display similar DNA-binding properties; therefore, we speculated that ets proteins other than Ets-1 also might bind these elements. Crude nuclear extracts of EL4.E1 cells were assayed to identify the protein(s) that potentially functions at the LVb element. The predominant binding activity was not Ets-1 but rather two independent DNA-protein complexes that comigrated in mobility shift assays. UV cross-linking and denaturing gel electrophoresis sized the two DNA-binding species, which we denoted p55 and p100. Immunoprecipitation combined with UV cross-linking identified p55 as the alpha subunit of GA-binding protein. The DNA-binding properties of p100 and several ets proteins were compared. Similarities suggested that p100 is also an ETS domain protein, possibly Elf-1. This strategy could be used to identify other ETS domain proteins in crude nuclear extracts. These findings suggest multiple ETS domain proteins could regulate gene expression of Mo-MuLV.
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PMID:Identification of ETS domain proteins in murine T lymphocytes that interact with the Moloney murine leukemia virus enhancer. 793 72

DAB486IL-2 is an IL-2-diphtheria toxin conjugate which was developed to be specifically cytotoxic to cells bearing high affinity IL-2 receptors. The high affinity IL-2 receptor is a heterodimer comprising p55 and p75 subunits. While the p75 subunit appears to be ubiquitously expressed among the common North American leukemias and lymphomas, the p55 subunit is more restricted in its expression. To broaden the therapeutic relevance of the DAB486IL-2 we have sought physiologically feasible inducers of the p55 IL-2 receptor subunit. This report describes that PHA, in vitro, induces the p55 IL-2 receptor subunit on initially p55-negative B-CLL cells and converts toxin-insensitive leukemia cells to a toxin-sensitive state.
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PMID:PHA induces IL-2 receptors on B-CLL cells and is a potential biological response modifier for the LIL-2-diphtheria toxin, DAB486IL-2. 810 88


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