Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Retinoic acid is known to cause the cell cycle arrest and myeloid differentiation of HL-60 myeloblastic leukemia cells. Evidence suggesting the possible involvement of the Fc gammaRII immunoglobulin receptor in mediating retinoic acid-induced growth arrest and differentiation of HL-60 cells is presented. HL-60 cells stably transfected with the delta205 mutant polyoma middle T antigen, a largely debilitated polyoma middle T antigen, are known to undergo accelerated retinoic acid-induced growth arrest and differentiation compared with parental HL-60 cells. Delta205 transfected cells were compared with parental HL-60 cells by differential display to identify differentially expressed genes, which are regulated downstream of delta205 and might facilitate cellular response to retinoic acid. Differential display revealed that the Fc gammaRII immunoglobulin receptor was differentially expressed. HL-60 cells express Fc gammaRIIA but not Fc gammaRIIB. In parental HL-60 cells, retinoic acid up-regulated Fc gammaRII expression, and Fc gammaRII membrane protein expression increased concomitantly with retinoic acid-induced cell cycle arrest and differentiation. Ectopic expression of Fc gammaRIIa1 in HL-60 cells retarded cellular progression through all phases of the cell cycle. For HL-60 cells stably transfected with Fc gammaRIIa1, onset of retinoic acid-induced growth arrest and differentiation occurred in fewer cell cycles than for parental HL-60 cells. Similar results occurred with 1,25-dihydroxy vitamin D3. Retinoic acid-induced tyrosine phosphorylation of various PAGE-detected protein bands in HL-60 cells was enhanced by cross-linking ectopically expressed Fc gammaRIIa1 receptor. The known retinoic acid-induced sustained activation of various mitogen-activated protein kinase signaling molecules, including extracellular signal-regulated kinase 2, src-like kinases, and adapter molecules, may in part reflect induced expression of Fc gammaRIIA, which is known to activate a similar ensemble of signaling molecules through its ITAM domain. The data suggest that retinoic acid induces increased Fc gammaRIIA expression, which is of functional consequence in eliciting growth arrest and differentiation.
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PMID:Retinoic acid-induced growth arrest and differentiation: retinoic acid up-regulates CD32 (Fc gammaRII) expression, the ectopic expression of which retards the cell cycle. 1247 67

Epstein-Barr virus (EBV)-immortalized lymphoblastoid cells express high levels of lymphotoxin and use this molecule as an autocrine growth factor. We hypothesized that the EBV-derived latent membrane protein 1 (LMP1) mediates lymphotoxin production by inducing NF-kappaB binding to the lymphotoxin promoter. We assessed lymphotoxin production, LMP1 expression, and NF-kappaB activation in Z-43 (EBV-positive lymphoblastoid cells), Daudi (EBV-positive Burkitt's cells), and 3A4 (EBV-negative Burkitt's cells containing a stably transfected tetracycline-inducible LMP1 construct). Z-43 cells expressed high levels of LMP1 (immunoblot) and lymphotoxin (ELISA); the EBV-positive Burkitt's lymphoma line Daudi expressed neither LMP1 nor lymphotoxin. Similarly, induction of LMP1 in the 3A4 cells (exposed to tetracycline) was accompanied by a 13-fold increase in lymphotoxin levels (ELISA) as compared to uninduced (LMP1-negative) cells. EMSAs demonstrated high levels of NF-kappaB activation in Z-43 and tetracycline-induced 3A4 cells, but much lower levels in the uninduced 3A4 cells. Exposure of these cells to Bay 11-7082 (an inhibitor of IkappaB phosphorylation and, therefore, NF-kappaB activation) abrogated NF-kappaB binding and lymphotoxin production in a dose-dependent manner in both Z-43 and 3A4 cells. Therefore, in our model system, autocrine lymphotoxin production is largely driven by NF-kappaB activation, which is in turn mediated by EBV-derived LMP1 signaling.
Leukemia 2003 Nov
PMID:Autocrine lymphotoxin production in Epstein-Barr virus-immortalized B cells: induction via NF-kappaB activation mediated by EBV-derived latent membrane protein 1. 1452 78

Podocalyxin-like protein (PCLP) is a sialomucin-type membrane protein structurally related to CD34 and endoglycan. It was first described in glomerular podocytes and endothelial cells. In mice, PCLP is present in haemangioblasts, and in both chicken and mice it is a marker of early haematopoietic stem cells and lineage-restricted haematopoietic progenitors. Its expression decreases during differentiation of haematopoietic cells. Of mature blood cells, only chicken and rat thrombocytes express PCLP protein. PCLP expression in human haematopoietic cells has not been studied. Here we demonstrate PCLP mRNA in human CD34+ cells, in lineage committed erythroid, megakaryocyte and myeloid progenitors, in K562 leukaemia cells, and in peripheral blood leucocytes. The mRNA expression level was higher in developing cells than in mature leucocytes. By Northern blotting and cDNA sequencing, the haematopoietic and renal PCLP mRNAs were identical. Of the mobilized CD34+ cells, 28% (mean; range 14-61%) expressed PCLP protein and the majority of PCLP+ cells were CD117+. Almost all of the K562 cells expressed PCLP protein. Surprisingly, PCLP protein was not detected in any mature blood cells. These results suggest that human PCLP may be a valuable marker for a subset of haematopoietic stem cells.
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PMID:Podocalyxin in human haematopoietic cells. 1500 70

The latent membrane protein-1 (LMP1) of Epstein-Barr Virus (EBV), saimiri transformation protein (STP) of Herpesvirus saimiri (HVS), and K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) are potent gammaherpesvirus oncogenes. To study the possible effects of double viral infection, we investigated the effects of oncogenic early proteins of DNA viruses E1A and E1B (adenovirus-5), E6 and E7 (human papillomavirus-16), HBx (hepatitis B virus), Tag (SV40), and gammaherpesviral oncogene during co-infection in human B-lymphoma (Ramos) and human T-cell leukemia (Jurkat) cell lines. HBx transactivated the promoters of LMP1, STP, and K1 the most, by about six-, three-, and twofold, respectively. Analyses of site-directed mutation and the heterologous promoter system showed that HBx activated the promoter activity of these genes via the NF-kappaB site. These results suggest that HBV (HBx) infection of cells previously infected by gammaherpesviruses transactivates their oncogenes, resulting in possible virus-related disease pathogenesis.
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PMID:Transcriptional activation of gammaherpesviral oncogene promoters by the hepatitis B viral X protein (HBx). 1506 83

We developed an assay allowing the detection and quantification of cell death after transient expression of apoptotic genes in B- and T-lymphocytes. For efficient gene transfer, B- and T-cells were electroporated under optimized conditions. To blind out the high background of non-transfected cells and cell death caused by the electroporation procedure itself, the green fluorescent protein (GFP) was co-transfected with the gene of interest. However, if the gene of interest was a potent apoptosis inducer, most successfully transfected cells were killed before GFP was expressed to levels sufficient for standard flow cytometry analysis or apoptosis assays. After staining of the transfected cells with propidium iodide (PI), very few GFP+/PI+ cells were detectable. To overcome this problem, the cell death rate induced by the transiently expressed gene was determined as the reduction of living green cells in the apoptotic versus a reference sample. This was achieved by an advanced flow cytometrical analysis quantifying the number of surviving green cells in normalised sample volumes directly relating to the number of initially transfected cells. Functioning of the assay was demonstrated by transient transfection of the potent apoptosis inducers TNF-receptor-associated death domain protein (TRADD) and a fusion protein of the transmembrane domain of the latent membrane protein 1 (LMP1) of Epstein-Barr virus and the signaling domain of TNF-receptor 1. We successfully applied the assay to the Burkitt lymphoma cell line BJAB and the T-leukemia cell line Jurkat.
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PMID:A novel assay to quantify cell death after transient expression of apoptotic genes in B- and T-lymphocytes. 1535 May 21

To investigate the possible mechanisms of nitric oxide (NO)-induced apoptosis in leukemia cell line HL-60, HL-60 cells in vitro were incubated with sodium nitroprusside (SNP), the in situ cell apoptosis quantitatively was assayed by TdT-mediated dUTP nick end labeling (TUNEL), the cell cycle DNA and proteins expression of Bcl-2, Bax, mitochondrial membrane protein (APO2.7) were analyzed by flow cytometry. The results showed that SNP induced HL-60 cell apoptosis in a dosage- and time-dependent manner. After exposure to SNP at the concentration of 1.0 mmol/L for 48 hours, the percentage of apoptosis HL-60 was (42.2 +/- 3.5)% for subG1 and (52.5 +/- 7.6)% for TUNEL respectively, and they are significantly higher than those in control and potassium ferricyanide (PFC) groups as same concentration. During the apoptosis process, it showed a decrease of Bcl-2 protein and an increase of Bax protein and mitochondrial membrane protein in HL-60 cell, proteins of Bcl-2, Bax and mitochondrial membrane were expressed in a dosage- and time-dependent manner too. In conclusion, during the process of SNP induced apoptosis in HL-60 cell, the expression of mitochondrial membrane protein was increased, Bcl-2 and Bax proteins may be important regulators.
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PMID:[Change of Bcl-2, Bax proteins and mitochondrial membrane protein on nitric oxide induced apoptosis in HL-60 cells]. 1536 28

The activation of natural killer (NK) cells leads to degranulation and secretion of cytotoxic granula. During this process, the lytic granule membrane protein CD107a becomes detectable at the cell surface. Based on this phenomenon, we have analyzed by a novel flow cytometry-based assay, the number and phenotype of NK cells responding to tumor targets. Using human leukemia and lymphoma cell lines, we observed a close correlation between CD107a surface expression and target cell lysis, indicating that NK cell cytotoxicity can be assessed by this method. The number of degranulating NK cells was closely related to the ratio of effector and target cells and showed a maximum at a ratio of 1:1. Moreover, we were able to show that the population of CD56(dim)/CD16(neg) NK cells is primarily responsible for the cytotoxic activity against tumor targets whereas neither CD56(dim)/CD16(pos) nor CD56(bright) NK cells degranulated in response to the cell lines. Our results indicate that the CD107a assay represents a promising new method for the quantification and characterization of cells exhibiting natural cytotoxicity.
Leukemia 2005 May
PMID:CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor targets. 1725 1

The differentiation of human endometrial epithelium is a dynamic event, which occurs throughout the menstrual cycle in preparation for pregnancy. The appearance of uterodomes (pinopods) in this regard was first introduced in rodents with an established pinocytotic function, whereas little evidence was available in humans in this context. This study was undertaken to identify the potential physiological roles of uterodomes in the implantation process. To address this, endometrial biopsies from early, mid- and late luteal phases of the menstrual cycle of 23 fertile female patients with regular menses were used. Scanning and transmission electron microscopies (SEM and TEM) as well as immunofluorescence and immunogold TEM were performed to study the morphological changes and the expression pattern of leukaemia inhibitory factor (LIF) at uterodomes. Our results illustrated a high level of LIF expression in the human uterodomes, which was colocalized with the well-known biochemical markers of exocytosis, including syntaxin-1, 25-kDa synaptosomal protein (SNAP-25) and vesicle-associated membrane protein-2 (VAMP-2). Our morphological and immunocytochemical findings illustrated a secretory function for human uterodomes for the first time. In conclusion, this novel function for uterodomes provides an important clue in detection of their physiological function(s) during the process of the plasma membrane transformation.
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PMID:Secretory role for human uterodomes (pinopods): secretion of LIF. 1612 73

Although interactions between cell surface proteins and extracellular ligands are key to initiating embryonic stem cell differentiation to specific cell lineages, the plasma membrane protein components of these cells are largely unknown. We describe here a group of proteins expressed on the surface of the undifferentiated mouse embryonic stem cell line D3. These proteins were identified using a combination of cell surface labeling with biotin, subcellular fractionation of plasma membranes, and mass spectrometry-based protein identification technology. From 965 unique peptides carrying biotin labels, we assigned 324 proteins including 235 proteins that have putative signal sequences and/or transmembrane segments. Receptors, transporters, and cell adhesion molecules were the major classes of proteins identified. Besides known cell surface markers of embryonic stem cells, such as alkaline phosphatase, the analysis identified 59 clusters of differentiation-related molecules and more than 80 components of multiple cell signaling pathways that are characteristic of a number of different cell lineages. We identified receptors for leukemia-inhibitory factor, interleukin 6, and bone morphogenetic protein, which play critical roles in the maintenance of undifferentiated mouse embryonic stem cells. We also identified receptors for growth factors/cytokines, such as fibroblast growth factor, platelet-derived growth factor, ephrin, Hedgehog, and Wnt, which transduce signals for cell differentiation and embryonic development. Finally we identified a variety of integrins, cell adhesion molecules, and matrix metalloproteases. These results suggest that D3 cells express diverse cell surface proteins that function to maintain pluripotency, enabling cells to respond to various external signals that initiate differentiation into a variety of cell types.
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PMID:Cell surface labeling and mass spectrometry reveal diversity of cell surface markers and signaling molecules expressed in undifferentiated mouse embryonic stem cells. 1617 23

Alemtuzumab is a humanized IgG1 kappa antibody directed against CD52, a glycosyl-phosphatidylinositol linked cell-membrane protein of unknown function. Herein, we demonstrate that alemtuzumab promotes rapid death of chronic lymphocytic leukemia (CLL) cells in vitro, in a complement and accessory cell free system. Using minimal detergent solubilization of CLL membranes, we found that CD52 colocalizes with ganglioside GM-1, a marker of membrane rafts. Fluorescence microscopy revealed that upon crosslinking CD52 with alemtuzumab+anti-Fc IgG, large patches, and in many cases caps, enriched in CD52 and GM-1 formed upon the CLL cell plasma membrane. Depletion of membrane cholesterol or inhibition of actin polymerization significantly diminished the formation of alemtuzumab-induced caps and reduced alemtuzumab-mediated CLL cell death. We compared alemtuzumab-induced direct cytotoxicity, effector cell-mediated toxicity and complement-mediated cytotoxicity of CLL cells to normal T cells. The direct cytotoxicity and observed capping was significantly greater for CLL cells as compared to normal T cells. Cell-mediated and complement-mediated cytotoxicity did not significantly differ between the two cell types. In summary, our data support the hypothesis that alemtuzumab can initiate CLL cell death by crosslinking CD52-enriched lipid rafts. Furthermore, the differential direct cytotoxic effect suggests that CD52 directed antibodies could possibly be engineered to more specifically target CLL cells.
Leukemia 2006 Feb
PMID:Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. 1634 Oct 49


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