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)

It was previously demonstrated that the 60,000 dalton (p60) precursor-like polyprotein containing murine p30 was a constituent of the feline leukemia virus pseudotype of Moloney sarcoma virus [m1MSV(FeLV)]. It is now shown that p60 is detected in cells of five mammalian species transformed by m1MSV, indicating that p60 is specified by this genome. Moreover, little or no murine p30 is detected in the m1MSV-transformed cells, suggesting that the murine group p30 antigenic reactivity of S + L- cells is ude to p60. Pulse-chase studies in cells producing m1MSV(FeLV) show that p60 is the largest polypeptide detectable during the pulse, and that intracellular p60 is not cleaved into smaller (for example, p30) polypeptides during chase periods of up to 10 hr. The lack of cleavage of p60 is in contrast to the properties of p30 precursors detected in cells containing replicating avian or mammalian RNA tumor viruses. The inefficient cleavage of intracellular p60 and the kinetics of appearance of murine p30 in extracellular m1MSV(FeLV) suggest that p60 cleavage to p30 occurs in cells shortly before virus release. While only p60 was detected in the m1MSV-transformed cells, p60 and p70 were detected in m3MSV-transformed cells, and no immunoprecipitable polypeptides were detected in HT-1 MSV-transformed cells. The observed differences in the intracellular polypeptide expression by each of the strains of MSV suggests differences in genetic content.
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PMID:Cells transformed by certain strains of Moloney sarcoma virus contain murine p60. 6 30

The synthesis and processing of feline leukemia virus (FeLV) polypeptides were studied in a chronically infected feline thymus tumor cell line, F-422, which produces the Rickard strain of FeLV. Immune precipitation with antiserum to FeLV p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to isolate intracellular FeLV p30 and possible precursor polypeptides. SDS-PAGE of immune precipitates from cells pulse-labeled for 2.5 min with [35S]methionin revealed the presence of a 60,000-dalton precursor polypeptide (Pp60) as well as a 30,000-dalton polypeptide. When cells were grown in the presence of the proline analogue L-azetidine-2-carboxylic acid, a 70,000-dalton precursor polypeptide (Pp70) was found in addition to Pp60 after a 2.5-min pulse. The cleavage of Pp60 could be partially inhibited by the general protease inhibitor phenyl methyl sulfonyl fluoride (PMSF). This partial inhibition was found to occur only if PMSF was present during pulse-labeling. Intracellular Pp70 and Pp60 and FeLV virion p70, p30, p15, p11, and p10 were subjected to tryptic peptide analysis. The results of this tryptic peptide analysis demonstrated that intracellular Pp70 and virion p70 were identical and that both contained the tryptic peptides of FeLV p30, p15, p11, and p10. Pp60 contained the tryptic peptides of FeLV P30, P15, and P10, but lacked the tryptic peptides of P11. The results of pactamycin gene ordering experiments indicated that the small structural proteins of FeLV are ordered p11-p15-p10-p30. The data indicate that the small structural proteins of FeLV are synthesized as part of a 70,000-dalton precursor. A cleavage scheme for the generation of FeLV p70, p30, p15, p11, and p10 from precursor polypeptides is proposed.
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PMID:Analysis of intracellular feline leukemia virus proteins II. Generation of feline leukemia virus structural proteins from precursor polypeptides. 19 17

The mouse plasmacytoma cell line, MOPC-460, produces both intracisternal and intracytoplasmic A-type particles when grown as a solid tumor. When these cells are grown either as an ascites tumor or in tissue culture, a third type of particle is produced extracellularly. This particle, the "myeloma-associated virus," is closely related to, and probably an alternate form of, the intracisternal A-type particle. The proteins present in these two types of particles were compared by tryptic peptide mapping. Both types of particles were found to contain essentially the same major proteins of 76,000 (p76), 68,000 to 70,000 (p68-70), and 45,000 (p45) daltons, in addition to varying amounts of smaller proteins. The relative proportions of all these proteins varied from preparation to preparation in an unpredictable way. The p45, p68, and p70 proteins all contained sequences found in p76, suggesting precursor-product relationships of p76 leads to p70 leads to p45 for solid tumor A-type particles and p76 leads to p68 leads to p45 for extracellular myeloma-associated virus. In addition, immune precipitation experiments have established that p76 contains at least some of the antigenic determinants characteristic of murine leukemia virus p30. This confirms earlier nucleic acid hybridization studies which indicated a moderate degree of relatedness between MOPC-460 A-type particles and several standard murine leukemia and sarcoma viruses. Taken together, our results provide evidence supporting the concept that MOPC-460 A-type particles may represent aberrant forms of C-type murine viruses.
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PMID:Characterization of the proteins of intracisternal type A and extracellular oncornavirus-like particles produced by MOPC-460 myeloma cells. 23 64

A cell line (BsT) established from neoplastic embryonal tissues of the platyfish (Xiphophorus maculatus) released spontaneously retrovirus-like particles. The particles have a buoyant density of 1.16 g/ml, a mean diameter of 100 nm and the morphology of immature retroviruses. The particle-associated proteins p70, p65, and p28 react with an antiserum directed against the major internal feline leukemia virus structural protein p27. The particles are associated with a reverse transcriptase. The purified enzyme has a molecular weight of about 70 kDa and prefers the template primers poly(rA):oligo(dT), poly(dC):oligo(dG), and poly(rC):oligo(dG) in the presence of Mn2+. The enzyme activity is inhibited by antibodies directed against the reverse transcriptase of feline leukemia virus and simian sarcoma virus. The particles contain a ribonucleic acid of about 70 S. In an endogenous reverse transcriptase reaction nucleic acids in the range of 0.2 to 0.4 kb were synthesized. In Northern blots with these nucleic acids as probe, three transcripts of about 8.5, 4.2, and 1.5 kb were detected in BsT cells. Southern blot analysis with the same probe demonstrates related sequences in the DNA of BsT cells and the platyfish and swordtail (Xiphophorus helleri). Hybridization experiments with the LTR-gag region of the feline leukemia virus show homologous sequences in the Xiphophorus genome.
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PMID:Isolation and characterization of a retrovirus from the fish genus Xiphophorus. 137 84

We report here the case of a 55-year-old patient with chronic granular lymphocyte disorder associated with moderate neutropenia. The majority of peripheral blood lymphocytes displayed a CD3-, CD8-, CD16+, CD56(NKH1)- phenotype. The patient's cells showed high spontaneous cytotoxic activity against K562 targets and developed the ability to kill the natural killer (NK)-resistant target Daudi following activation with interleukin 2 (IL-2). Simultaneously, IL-2 induced proliferation of these cells, albeit to a low level. The effects of IL-2 are likely to be mediated through the IL-2R beta chain (p70) which is expressed on these cells in the absence of the IL-2R alpha chain (p55, Tac). IL-4 was demonstrated to be inhibitory of both the cytotoxic and proliferative effects of IL-2. Thus, despite an unusual CD56- phenotype, the expanded lymphocyte population in this patient display functional and phenotypic properties of normal, non-activated NK cells. These cells probably represent the counterpart of a minor NK cell subpopulation, present in normal individuals at a low frequency, and which has never been fully characterized functionally. In addition, we show that the cytolytic activity of this NK cell population can be blocked in vitro in the presence of a cAMP analog or of theophylline, possibly providing new means of investigating the role of NK cell cytotoxicity on the pathogenesis of associated symptoms in such patients.
Leukemia 1992 May
PMID:In vitro responsiveness to interleukins and theophylline of CD16+, CD56- natural killer cells in a patient with chronic granular lymphocyte disorder. 137

The effect of phorbol myristate acetate (PMA) on the expression of interleukin 2 receptors (IL-2R), production of IL-2 and IL-2-dependent proliferation of acute lymphoblastic leukemia T cells (T-ALL cells) from 10 patients was studied. First, the effect of PMA on the expression of cell surface markers was assessed: a decrease of CD3 and CD4, and an enhanced expression of CD8 molecule were observed on T-ALL cells. Moreover, PMA exhibited an heterogenous effect on various activation-associated molecules such as a decreased expression of transferrin receptor and T10 molecule and an induced expression of 4F2 and CD9 molecules. It is known that functional high-affinity IL-2R are composed of at least two IL2 binding molecules, the alpha (p55) and beta (p70) chains. We found that PMA induced the expression of both IL-2R alpha and IL-2R beta chains, as well as IL-2 production by T-ALL cells. These effects were time- and dose-dependent. Cross-linking experiments with 125I-labelled recombinant IL-2 (125I-rIL-2) revealed both p55 (IL-R alpha) and p70 (IL-2R beta) IL-2-binding polypeptides, whereas binding equilibrium assays on PMA-treated cells demonstrated the presence of a low number (31-413) of high-affinity binding sites/cell in five out of six cases analysed, as well as intermediate affinity IL-2R (1234-3919 sites/cell) in four out of six cases, according to the time of incubation with PMA. In two cases tested high-affinity IL-2R on PMA-treated T-ALL cells could internalize 125I-rIL-2 at 37 degrees C. PMA alone enhanced the spontaneous proliferation of T-ALL cells in three cases, whereas a clear synergy between IL-2 and PMA could be detected in three patients' cells. Moreover, exogenous rIL-2 enhanced cell proliferation of PMA-preincubated T-ALL cells in four cases studied. Taken together, these observations indicate that a short-term incubation of T-ALL cells with PMA can activate the IL-2/IL-2R system on these cells without inducing strong modifications of their differentiation status. These results thus suggest that this system may be involved in the proliferation process of some activated immature T cells.
Leukemia 1992 Apr
PMID:Phorbol myristate acetate-induced expression of high-affinity interleukin 2 receptors and production of interleukin 2 by human acute lymphoblastic leukemia T cells. 158 92

We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody (MoAb), designated Mik-beta 1, which has been recently developed. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis. These results indicate that flow cytometric analysis using MoAbs, anti-Tac, and Mik-beta 1 is useful for detecting the expression of the IL-2R chains.
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PMID:Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells. 238 56

Abnormal expression of the low-affinity receptor for interleukin-2 (IL-2R) is a characteristic of the HTLV-I (+) leukemic T cells in adult T-cell leukemia (ATL). Despite the expression of IL-2R bearing Tac antigen (IL-2R/p55), leukemic cells of the majority of ATL patients do not proliferate in response to IL-2. In the human NK cell line, YT, as well as in ATL-derived T cells, the co-expression of IL-2R/p55 and the second IL-2R without the Tac epitope (IL-2R/p70) is required to produce high-affinity IL-2R. To study the effect of HTLV-I on both of the IL-2Rs, we transfected a fragment of HTLV-I containing the p40X gene into YT cells. One of the 2 transfected YT clones (YT/pX-5.1) had an increased level of expression of IL-2R/p55. In contrast, expression of IL-2R/p70 was unaffected, as determined by Scatchard analysis and the cross-linking study using 125I-IL-2. Our results show that the T-cell phenotype is not required for induction of IL-2R/p55 by p40X. We suggest that HTLV-I infection induces a disproportionate induction of IL-2R/p55 without significant enhancement of IL-2R/p70 expression, resulting in the predominant expression of low-affinity IL-2R in ATL. IL-2R/p70 may be a critical parameter determining the IL-2 reactivity of HTLV-I-infected T cells as well as of normal lymphocytes.
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PMID:Differential effects on expression of IL-2 receptors (p55 and p70) by the HTLV-I pX DNA. 289 42

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

The rate of the maturation process of avian myeloblastosis virus experimentally estimated on the basis of genomic viral RNA conversion and morphological transition of virions was mathematically analysed. Three mathematical models were suggested and fitted to experimental data. It was found that: (a) model of simple kinetics (Model 1) does not agree with experimental data. Therefore, two hypotheses were considered in further mathematical modelling: (b) virions are identical in time of budding: maturation is dependent on the presence of a virion component which is degraded with time (Model 2). This model agrees with experimental data in all stages of the maturation process. (c) Virions are released from cells at different stages of assembly (Model 3). This model differs from experimental data especially in early stages of maturation. The hypothesis used for the construction of Model 2 seems to be the most plausible to explain the maturation process and is in agreement with data of murine leukemia virus maturation which was found to be accomplished by cleavage of p70 precursor protein.
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PMID:Mathematical analysis of the oncornavirus maturation process (virion RNA conversion and morphological condensation). 721 46


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