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)

To determine the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during hematopoiesis and on leukemic cells, monoclonal antibodies were raised by immunizing mice with cells expressing high levels of human GMR alpha. A pool of five antibodies isolated from three different mice was used to characterize GMR alpha. This antibody pool (anti-GMR alpha) immunoprecipitated a protein with the expected molecular weight of GMR alpha from COS cells transiently transfected with the GMR alpha gene. In factor-dependent cells, GMR alpha existed as a phosphoprotein. However, its phosphorylation was not stimulated by the presence of GM-CSF. Anti-GMR alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone marrow cells and inhibited the binding of iodinated GM-CSF to its receptor. Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry. GMR alpha was readily detectable on both blood monocytes and neutrophils. In adherence-depleted normal bone marrow, two separate populations expressed GMR alpha. The most positive cells were predominantly macrophages, whereas the cells that expressed less GMR alpha were largely myelocytes and metamyelocytes. A small population of lin-CD34+ or CD34+CD38- cells also expressed GMR alpha, but they were not capable of significant growth in colony-forming assays. In contrast, the majority of lin-CD34+ and CD34+CD38- cells were GMR alpha-, yet they produced large numbers of myeloid and erythroid colonies in the same assay. Malignant cells from patients with leukemia were also tested for GMR alpha expression. All of the myeloid leukemias and only rare lymphoid leukemias surveyed tested positive for GMR alpha. These results show that anti-GMR alpha is useful for the functional characterization of the GMR alpha and for the detection of myeloid leukemia and that GMR alpha is expressed on certain lineages throughout hematopoietic development; however, progenitors that express the receptor may have a reduced capacity to proliferate in response to hematopoietic growth factors.
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PMID:Expression and function of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit. 799 31

Epstein-Barr Virus (EBV) causes infectious mononucleosis in normal adolescents and malignant B lymphocyte proliferation in immune compromised patients, in marmosets, or upon transfer of infected human B lymphocytes into SCID mice. EBV is also etiologically associated with African Burkitt's lymphoma, Hodgkin's Disease, and nasopharyngeal cancer. EBV transformed, latently infected B lymphocytes contain EBV episomes and eight virus encoded proteins. Six are nuclear proteins (EBNAs) and two are the integral membrane proteins, LMP1 and LMP2. These eight proteins are presumed to mediate latent virus infection or B lymphocyte proliferation and are thus under intense scrutiny. Besides EBNA1, which is required for episome maintenance, LMP1 and LMP2, are the two transformation associated proteins that are most consistently detected in EBV related malignancies, and the LMP2 message is the only message detected in PCR analysis of B lymphocytes from individuals harboring EBV latent infections. LMP2 associates with src family tyrosine kinases, a 70 kda cell phosphoprotein, LMP1 and several other unidentified cell proteins. LMP1 is a key mediator of EBV's effects on inducing B lymphocyte activation and adhesion molecules and is a transforming oncogene in rodent fibroblasts. The association of these two EBV encoded membrane proteins could create a macromolecular complex mediating constitutive B lymphocyte activation through normal cell signal transduction pathways. LMP2 might may control activation of lytic replication or down regulate the activation state of EBV infected cells allowing persistence in the human host.
Leukemia 1994 Apr
PMID:Biochemical and genetic studies of Epstein-Barr virus latent membrane protein 2. 815 3

SCG10 is a neuronal growth-associated protein that shares an amino acid sequence similarity with an 18- to 19-kDa phosphoprotein named stathmin (also called p19, p18, Op18, pp17, prosolin, pp20, 19K, and leukemia-associated phosphoprotein, Lap18), which is more broadly expressed in a variety of cell types of the neural, immune, and reproductive systems. The sequence similarity has suggested that SCG10 and stathmin have been derived from structurally and evolutionarily related genes. To explore the structural and evolutionary relationships between these genes, we have isolated a series of cosmid and phage clones that covers the entire region of the mouse stathmin gene and most of the mouse SCG10 gene. The SCG10 transcription unit spans at least 30 kb, while the stathmin gene is 6 kb in length. Both genes consist of five exons, and many of the intron/exon boundaries fall into the homologous regions of conserved domains of these two proteins. However, the promoter-proximal regions are distinct in the two genes, suggesting that they have evolved by fusion of the duplicated coding exons to unique promoters. Southern blot analysis indicates that SCG10 mRNA is encoded by a single gene in the mouse genome, while stathmin cDNA probes detect multiple genes. Chromosome mapping experiments reveal that the SCG10 gene is localized at the proximal region of mouse chromosome 3 and is linked to Il-7, while the stathmin gene loci are distributed to three chromosomes; the authentic stathmin gene lies on chromosome 4, whereas the loci on chromosomes 9 and 17 are likely to be pseudogenes. These data are consistent with the idea that the neuron-specific SCG10 gene evolved by duplication and modification of the more broadly expressed stathmin/Lap18 gene.
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PMID:Molecular diversity of the SCG10/stathmin gene family in the mouse. 828 40

The retinoblastoma gene (RB) is a growth suppressor gene on the human chromosome 13q14. It encodes a 105 kDa phosphoprotein (p105), with DNA-binding capacity. P105 is thought to be involved in cell cycle control. Inactivation of RB is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung cancer. In this study we looked at the RB-structure and expression in cell lines and primary lymphoma samples from patients with high grade non-Hodgkin's lymphoma (NHL). Forty five primary high grade NHL, the B-lymphoblastoid cell line IM-9 and the NHL cell line WSU-NHL were studied for RB structure by Southern blotting and for RB-expression by Northern blotting, Western blotting and immunocytochemistry. In all experiments freshly cryopreserved material was used. Southern and Northern experiments were performed with the 0.9 kb and 3.8 kb RB-cDNA probe. For the detection of p105 two different anti-p105-monoclonal antibodies were used in immunocytochemistry and Western blotting experiments. No RB mRNA and no p105 could be found in IM-9 cells. Twenty six high grade NHL samples (58%) showed no p105 expression. In the subgroup of centroblastic lymphomas 16 out of 21 and in Burkitt's lymphomas five out of eight showed no p105-expression. P105 expression is absent in 58% of high grade NHL, particularly in centroblastic and Burkitt's lymphomas, suggesting that inactivation of RB may play a crucial role in the pathogenesis of high grade NHL.
Leukemia 1994 Jan
PMID:Altered expression of the retinoblastoma gene product in human high grade non-Hodgkin's lymphomas. 828 6

One major substrate protein was phosphorylated with [gamma-32P]GTP in membranes of human leukemia (HL-60) cells. The phosphoprotein comigrated with beta-subunits of heterotrimeric GTP-binding proteins (G proteins) in different gel systems. Upon solubilization of the phosphorylated membranes, the phosphoprotein could be immunoprecipitated by a G protein beta-subunit-specific antiserum. The beta-subunit phosphorylation was transient and was found to be specific for GTP and its analog, guanosine 5'-O-(gamma-thio)triphosphate. When phosphorylated membranes were incubated with various nucleotides, the bound phosphate was specifically removed by GDP, suggesting that the phosphate can be retransferred onto GDP. Divalent cations, preferentially Mg2+ and Mn2+, were required for both phosphorylation and dephosphorylation. The phosphorylation was stable against treatment with NaOH but sensitive to treatment with heat, HCl, and hydroxylamine. Moreover, treatment of the membranes with the histidine-modifying agent, diethyl pyrocarbonate, resulted in a loss in phosphate incorporation. The data suggest that G protein beta-subunits are involved in a guanine nucleotide-specific enzymatic activity transferring the gamma-phosphate from GTP to GDP, presumably at G protein alpha-subunits, via a phosphohistidine intermediate.
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PMID:Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein beta-subunits. Characterization of the phosphorylated amino acid. 834 88

Oncoprotein 18 (Op18) is an 18 kDa intracellular phosphoprotein that appears to be up-regulated in certain neoplastic cells. In the present report we have analysed the expression of Op18 in samples of human hematopoietic disorders, mainly leukemias and lymphomas. For this purpose we have developed reagents allowing quantitative Western-blot analysis, and quantification of Op18 on the single cell level by flow cytometric analysis. The data demonstrates that a significant fraction of all lymphoma and leukemia cases express Op18 at levels that are several-fold higher than the Op18 levels ever found in benign proliferating tissue, such as bone marrows in remission and reactive lymph nodes. Thus, the results establish on the single cell level that Op18 is frequently expressed at abnormal levels in lymphoid and myeloid malignancies. Flow cytometric analysis revealed a striking qualitative and quantitative heterogeneity in Op18 expression between patients with lymphoma or leukemia. Moreover, our analysis demonstrates that the abnormal cellular levels of Op18 expression frequently found in high grade lymphoma and acute leukemia samples do not correlate with an increased fraction of cells in S phase. Finally, we also present an example of dramatic changes in Op18 expression pattern in bone marrow cells during the progression of a chemo-resistant acute leukemia.
Leukemia 1993 Oct
PMID:Expression of oncoprotein 18 in human leukemias and lymphomas. 841 15

Activation of protein kinase C results in phosphorylation of a 19-kDa protein termed 19K. Isolation and sequence analysis of a cDNA encoding the 19K protein revealed that this protein has been studied in other systems under different names. The name oncoprotein 18 (Op18) has been proposed on the basis of a postulated up-regulation in neoplastic cells. In the present report we adopt the designation Op18 for the 19K protein, and quantify this phosphoprotein in a series of leukemia/lymphoma cell lines, a panel of non-transformed cells and some terminally differentiated cell types. For this purpose we have developed reagents allowing quantitative Western-blot analysis, and quantification of Op18 on the single cell level by flow cytometric analysis. The data demonstrates a pronounced up-regulation of the Op18 protein in most leukemia/lymphoma cell lines. The HPB-ALL cell line provided the most extreme case and expressed 7 x 10(6) Op18 molecules/cell, which compares with 0.65 x 10(6) Op18 molecules/cell in non-transformed lymphoblastoid cells. The expression of Op18 appears to be restricted to cell types with proliferative potential, but it is clear from our results that up-regulation of Op18 is uncoupled from cellular proliferation. Moreover, by employing an Epstein-Barr virus based shuttle vector, we expressed Op18 cDNA in lymphoblastoid cells. This resulted in a three to fourfold up-regulation of Op18 that did not have any detectable consequences for cell-surface phenotype or cell size. However, increased expression of Op18 resulted in a partial inhibition of cell proliferation. Taken altogether, the results suggest that up-regulation Op18 levels in leukemia/lymphoma cells are strongly associated with, but not a direct cause of tumour progression.
Leukemia 1993 Apr
PMID:Quantitative analysis of the expression and regulation of an activation-regulated phosphoprotein (oncoprotein 18) in normal and neoplastic cells. 846 35

Vpu is a 16-kDa membrane-associated phosphoprotein that is expressed from the same, singly spliced message as the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor, gp160. Previous studies suggest that Vpu functions in the late stages of viral replication, possibly in virus egression from the cell. Recently, it has been demonstrated that Vpu functions to allow gp160 to be more efficiently processed by disrupting CD4-gp160 complexes generated by transfection of HeLa cells. We show here that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression. This reduction persists when HIV-1 particles are pseudotyped with the HIV-2 or amphotropic murine leukemia virus envelope glycoprotein. Pulse-chase analysis of HIV-1 capsid protein (p24) in the absence of CD4 and envelope glycoprotein demonstrates that the rate of virus release is reduced when Vpu is not expressed. Our findings indicate that Vpu has a function involving particle release not dependent on CD4 or envelope glycoprotein expression.
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PMID:Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function. 851 Feb 20

The Tax protein from human T-cell leukemia virus type I (HTLV-I) is a 40-kDa phosphoprotein capable of activating transcription from its own long terminal repeat (LTR), as well as increasing the transcription of cellular genes. Transcriptional activation of the HTLV-I LTR has been demonstrated via a cyclic-AMP-responsive element within the 21-bp Tax-responsive elements of the LTR. Phorbol esters also upregulate expression via the LTR. Since phosphorylation of Tax may play a role in these processes, we investigated the relative effects of kinase-stimulating agents on 32P incorporation into Tax. Our studies demonstrated that the phorbol ester 4 beta-phorbol-12 beta-myristate-13 alpha-acetate greatly stimulated Tax phosphorylation in a time- and dose-dependent manner. In contrast, 8-bromoadenosine 3'-5'-cyclic monophosphate induced little stimulation of Tax phosphorylation. Tax phosphorylation occurred only on serine residues and was mapped to a single tryptic fragment in both Tax-producing human lymphocytes and mouse fibroblast cells.
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PMID:Phorbol esters modulate the phosphorylation of human T-cell leukemia virus type I Tax. 851 Feb 30

Herpes simplex virus type 1 (HSV-1) Us11 protein, a true late gene product packaged within the virion, is delivered into cells after infection, exhibits a nucleocytoplasmic localization at early times, and later accumulates in the nucleoli. This RNA-binding basic phosphoprotein, capable of oligomerization, is supposed to be involved in post-transcriptional regulation of gene expression after HSV-1 infection. Expression of human T-cell leukaemia/lymphoma virus type-I (HTLV-I) and of human immunodeficiency virus type 1 (HIV-1) is post-transcriptionally regulated by Rex and Rev, respectively. These proteins are required for the cytoplasmic expression of unspliced gag-pol and singly spliced env transcripts. Here we show that HSV-1 Us11 protein is able to bind Rex- and Rev-responsive elements and to transactivate envelope retroviral glycoprotein expression.
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PMID:Post-transcriptional transactivation of human retroviral envelope glycoprotein expression by herpes simplex virus Us11 protein. 853 83


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