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 DNA fragment of the herpes simplex virus type 1 genome encoding glycoprotein C (gC-1) has been cloned into different eukaryotic expression vectors for transient and stable expression of the glycoprotein in a number of cell lines. All of these expression vectors use a non-HSV promoter, such as the adenovirus major late promoter or murine leukemia virus long terminal repeat promoter to express gC-1 in COS and CHO cells or 3T3 cells. The gC-1 protein synthesized was fully glycosylated with both N- and O-linked oligosaccharides. Synthesis of the mature 120K gC-1 glycoprotein involved partially glycosylated 100K and 105K proteins and the non-glycosylated 70K protein as intermediate molecules. Immunofluorescence studies showed that the expressed gC-1 was localized intracellularly in the nuclear envelope as well as on the cell surface. The expressed gC-1 was biologically active and could act as a receptor for the complement component C3b in the absence of other HSV proteins.
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PMID:Expression from cloned DNA of biologically active glycoprotein C of herpes simplex virus type 1 in mammalian cells. 215 2

We discovered that the common acute lymphoblastic leukemia antigen, CALLA (CD10), was identical to human neutral endopeptidase 3.4.24.11 (NEP), a Zn-binding glycoprotein with an extracellular active site capable of hydrolyzing several biologically active peptides. In this study we compare the expression of CALLA/NEP in terms of antigenic density and enzymatic activity at the cell surface and of messenger RNA (mRNA) levels on granulocytes, leukemic cells, and CALLA-transfected COS-1 cells. Mature granulocytes, the only readily available source of normal human CALLA, express relatively low but constant levels of antigen, NEP activity (3.5 pmol/min/10(6) cells), and mRNA. The two major CALLA-mRNA species of 6.5 kb and 3.8 kb, observed to date in a variety of cells and tissues, were also found in four independent granulocyte preparations. With leukemia cell lines, a correlation was established between the density of CALLA antigen and the level of enzymatic activity (3.4 to 21.0 pmol/min/10(6) cells). This paper constitutes the first report of NEP activity on blast cells derived from patients with non-T acute lymphoblastic leukemia (ALL); the levels of activity were variable (1.5 to 35.9 pmol/min/10(6) cells for six cases) but correlated with the level of CALLA assessed by flow cytometry. Heterogeneous levels of expression of the CALLA-mRNA species were also observed in non-T ALL cases that correlated with the level of CALLA expression at the surface of these cells. Very high levels of NEP activity were achieved by transfecting COS-1 cells with pSV-CALLA; 20% of the transfected cells were CALLA+ and expressed 550 pmol/min/10(6) cells. Extracts prepared from COS-1 cells transfected with pSV-CALLA (carrying human NEP cDNA) and pSVENK19 (carrying rabbit NEP-cDNA), respectively, gave Michaelis constant (Km) values of 50 mumol/L and similar inhibition curves with thiorphan. Thus the recombinant proteins encoded by these two genes have similar enzymatic properties, confirming the high degree of their structural relatedness. The expression of high levels of CALLA/NEP on COS-1 cells should allow the use of this system to test the effects of specific mutations on activity and might lead to the understanding of the role of CALLA in the onset and/or progression of leukemia.
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PMID:Comparative levels of CALLA/neutral endopeptidase on normal granulocytes, leukemic cells, and transfected COS-1 cells. 216 7

A cDNA clone encoding the human lymphocyte differentiation Ag CD38 was isolated from a mixture of four different lymphocyte CDNA libraries expressed transiently in COS cells and screened by panning with mAb. Transfected COS cells expressed a surface protein of Mr 46,000 that was similar to the native CD38 molecule expressed on the B cell line Daudi and the T cell leukemia HPB-ALL and which was recognized by each of the CD38 specific mAb HIT-2, T16, T168, HB7, 5D2, ICO-18, and ICO-20. The CD38 cDNA sequence predicts an unusual 30-kDa polypeptide with a short N-terminal cytoplasmic tail, and a carboxyl-terminal extracellular domain carrying the four potential N-linked glycosylation sites. The absence of significant homology with other known surface Ag including members of the Ig superfamily ruled out the possibility that CD38 was the human homologue of the murine Qa2 molecule as has been suggested previously. PvuII digests of human genomic DNA revealed a polymorphism linked to the CD38 gene.
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PMID:Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. 231 35

Specific [3H]retinoic acid (RA)-binding sites in nuclear and cytosolic extracts prepared from human myeloblastic leukemia HL-60 cells have been detected by sucrose density gradient sedimentation and size-exclusion high-performance liquid chromatography (HPLC) analyses. This RA-binding activity migrated as a single peak with an apparent molecular weight of 50,000 and greater than 95% of the total binding activity was associated with the nuclear extract. Nuclear extracts prepared from COS-1 cells transfected with an expression vector for the nuclear RA receptors RAR alpha or RAR beta were enriched (20- to 100-fold) with a RA-binding activity that coeluted by size-exclusion HPLC with the putative RAR from HL-60 cells. The HL-60 nuclear receptor exhibited high-affinity binding of RA and its benzoic acid analogs Ch55, Ch30, Ro 13-7410, and SRI 6409-40 and low-affinity binding of retinol, Ro 8-8717, and SRI 5442-60, correlating well with the biological activity of these compounds in HL-60 cells. Saturation binding and Scatchard plot analyses of the binding of RA to the nuclear HL-60 receptor yielded an apparent dissociation constant of approximately 0.46 nM and 1400 +/- 100 receptor sites per cell. Northern blot analyses of poly(A)+ RNA with cDNA probes specific for RAR alpha and RAR beta indicated that HL-60 cells contain predominantly transcripts encoded by the RAR alpha gene. Our results suggest that the observed nuclear RA-binding activity in HL-60 cells might mediate the action of RA in these cells.
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PMID:Identification and characterization of nuclear retinoic acid-binding activity in human myeloblastic leukemia HL-60 cells. 254 90

Lymphocyte transformation/activation is accompanied by the induction of a variety of the inducible receptors associated with the activation antigens. The p55 chain of the interleukin-2 receptor (IL-2R/p55) recognized by anti-Tac monoclonal antibody (mAb) is expressed on activated T and B cells as well as natural killer (NK) cells. IL-2R/p55(Tac) is constitutively expressed on T4(+) T cells transformed by human T-lymphotropic virus I (HTLV-I), which is a causative agent for adult T-cell leukemia (ATL). Low affinity Fc receptor for IgE (Fc epsilon R2/CD23) is another inducible receptor binding IgE and is expressed on various hematopoietic cell types. While the physiological expression of Fc epsilon R2 and its soluble form (IgE Binding Factor; IgE BF) is variably regulated by cytokines and IgE, there is a constitutive expression of Fc epsilon R2 on Epstein-Barr virus (EBV) transformed B cell lines and some of HTLV-I (+) T cell lines. ATL-derived factor (ADF) has been characterized as an IL-2R/p55(Tac) inducing factor derived from HTLV-I(+) T cell lines. Purification of ADF protein and the cDNA cloning proved that ADF is closely related to the autocrine growth factor produced by an EBV(+) B cell line 3B6 (H. Wakasugi and T. Tursz) and belonging to the family of thiol reducing co-enzyme thioredoxin which is involved in many biological reactions. Recombinant ADF produced by COS cells and E. coli showed both IL-2R inducing and reducing activities. We will discuss the biological roles of ADF in viral and normal lymphocyte activation and transformation in relation to the receptor gene activation.
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PMID:IL-2 receptor and Fc epsilon R2 gene activation in lymphocyte transformation: possible roles of ATL-derived factor. 297 20

The 28,000 mol. wt. polypeptide (p28) of adult T-cell leukaemia-associated antigen encoded by the 24S defective human T-cell leukaemia virus (HTLV-I) is associated with protein kinase activity. We have determined the nucleotide sequence of this defective HTLV-I provirus and found that it contains a portion of the gag gene (p19 and part of p24), the pX region, and two long terminal repeats, one at each end. The predicted p28 gag-pX fused protein consists of 190 amino acids and its mol. wt. was calculated as 21,055. The results of peptide mapping analysis showing that p28 contains p19 supported the nucleotide sequence data. That p28 was encoded by this defective provirus was also demonstrated by transient expression of p28 polypeptide in COS 7 cells transfected with a recombinant plasmid containing a simian virus 40 early promoter and the p28-coding region of the 24S HTLV-I.
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PMID:Structural analysis of p28 adult T-cell leukaemia-associated antigen. 301 50

The coding regions of murine interferon-alpha (IFN-alpha) genes were combined with promoter and 3'-noncoding sequences from other eukaryotic genes. Transient expression of these fusion genes was achieved in monkey COS cells and in a mouse cell line (TOP cells) expressing polyoma virus (Py) large T antigen constitutively. The efficiency of the different expression plasmids was determined by measuring the amount of IFN secreted into the medium. Replacement of the 3'-noncoding region of an IFN-alpha gene by that of the rabbit beta-globin gene resulted in a fourfold higher IFN-alpha production. The SV40 early promoter and the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR) produced similar amounts of IFN-alpha in COS cells. However, a tandem combination of the SV40 enhancer/early promoter and the mouse metallothionein-I promoter appeared fivefold more active than the SV40 early promoter. In TOP cells the MoMLV LTR was found to be threefold more active than the Py early promoter.
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PMID:Transient expression of murine interferon-alpha genes in mouse and monkey cells. 302 4

We show that IgE-binding protein (epsilon BP) is found primarily in the cytoplasm of rat basophilic leukemia (RBL) cells and COS-1 cells transfected with epsilon BP cDNA. Antibodies to a synthetic peptide internal to epsilon BP were generated that specifically recognized epsilon BP by protein immunoblotting. These antibodies also bind the surface of RBL cells. Surprisingly, blot hybridization analysis of RNA from nine various normal rat tissues showed that the epsilon BP gene is transcribed in all the tissues tested as well as in a mouse macrophage-like cell line.
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PMID:IgE-binding protein. Subcellular location and gene expression in many murine tissues and cells. 313 67

Activation of the oncogenic potential of c-abl proto-oncogene has been correlated with the activation of its tyrosine kinase activity. The oncogenes derived from c-abl, e.g., gag/v-abl in Abelson murine leukemia virus or bcr/abl in chronic myelogenous leukemia, lack N-terminal coding sequences of the normal c-abl gene. In mouse and human cells, two sets of N-terminal amino acids encoded by 5'-variable exons are found in c-abl proteins. To assess the importance of N-terminal deletion in the activation of c-abl tyrosine kinase, a full length or an N-terminal deleted c-abl protein was expressed in bacteria and in monkey COS cells. Measurements of the autokinase activity of these two c-abl proteins showed that deletion of the N-terminal amino acids led to a three to five fold increase of the c-abl tyrosine kinase activity. Thus, the N-terminal deletion is important in the activation of c-abl proto-oncogene.
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PMID:Negative regulation of c-abl tyrosine kinase by its variable N-terminal amino acids. 314 98

Autonomous production of a required growth factor is one mechanism by which a cell may become tumorigenic. Several leukaemias have been described which secrete growth factors which may be involved in autocrine stimulation of cell proliferation. One of these leukaemias is WEHI-3B, a myelomonocytic leukaemia that constitutively produces interleukin-3 (IL-3). Cloning of the IL-3 gene has enabled us to investigate possible genetic changes in this gene in WEHI-3B cells which may have resulted in autonomous production of growth factor. We have shown that one of the IL-3 genes in WEHI-3B has been rearranged, as a result of the insertion of a 5.1 kilobase intracisternal A-type particle genome head to head with the 5' end of the IL-3 gene, 215 bases upstream of the IL-3 TATA box. The rearranged gene, when cloned into a lambda EMBL3A vector, could readily be expressed in COS-1 monkey cells, whereas the normal gene, in the same vector, was silent. Thus the insertion of the endogenous retroviral element has resulted in abnormal expression of the IL-3 gene and is postulated to have been a key genetic change in the development of this leukaemia. In an attempt to experimentally construct IL-3 producing leukaemias, IL-3 responsive FDC-P1 and 32D cl-23 cells were transfected with a retroviral expression vector containing the IL-3 gene. This resulted in autonomous production of IL-3 and continuous proliferation of the transfected cells. As a result of transfection, the FDC-P1 and 32D cl-23 cells became leukemogenic demonstrating the oncogenic potential of abnormal expression of IL-3. The autocrine nature of the experimental leukaemias was demonstrated by blocking their proliferation with an IL-3 neutralising antiserum. Similarly treated cultures of normal bone marrow cells also produced IL-3 and could be maintained for several months after transfection but were not leukemogenic. The factor-dependent cell lines are unable to differentiate in the presence of known CSF's and presumably have undergone other genetic changes which allow them to become leukemogenic when autocrine-stimulated. In contrast, the transfected bone marrow cells could differentiate and form colonies containing mature granulocytes and macrophages. The non-tumorigenic behaviour of the transfected bone marrow cells is consistent with the concept that several other genetic changes which effectively block differentiation are required for development of tumorigenicity in these cells.
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PMID:Abnormal expression of interleukin-3 and leukaemia. 331 Aug 51


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