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)

PCR analysis and Western blotting revealed the expression of the mineralocorticoid receptor (MCR) and the epithelial sodium channel (ENaC) genes at the level of RNA, DNA, and protein in several leukemic cell lines, fibroblasts from human cornea, and epithelial cells from ocular tissues. Following immunofluorescence, the MCR appeared to be primarily nuclear whereas the ENaC was almost exclusively membrane-bound. Paradoxically, the MCR-specific antagonist ZK 91587 actually stimulated the multiplication of human erythroblastic leukemia cells, contrary to the inhibitory effect of the antagonist RU 26752 on the multiplication of corneal fibroblasts; both effects were opposed by aldosterone. In quantitative PCR, both basal and aldosterone-induced levels of ENaC were diminished by ZK 91587 in the corneal fibroblast, in contrast to the stimulation observed in the retinal pigmentary epithelium. Thus, contrary to the existing notions, (a) antimineralocorticoids can act both as agonists and antagonists, and (b) the receptor-mediated action of mineralocorticoids on the sodium channel is not restricted to the epithelial cell.
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PMID:Paradoxical effects of mineralocorticoids on the ion gated sodium channel in embryologically diverse cells. 1077 7

We studied the expression of the mineralocorticoid receptor (MCR), and of the amiloride-sensitive sodium channel (ASSC) regulated by the MCR, in human leukemic cell lines. Cell extracts from TF1 (proerythroblastic), HEL (human erythroblastic leukemia) and U937 (myeloblastic) cell line were positive for the ASSC, as a 82 kDa band in Western blots developed with the aid of a polyclonal antibody raised against the peptide QGLGKGDKREEQGL, corresponding to the region 44-58 of the alpha subunit of the epithelial sodium channel (ENaC) cloned from rat colon, linked to KLH. The polyclonal antibody against the MCR revealed a single band of about 102 kDa in extracts from HEL and TF1 cells. The immunofluorescent labelling of the MCR in all cell lines showed a nucleocytoplasmic localization of the receptor but the ASSC was exclusively membrane-bound and these results were confirmed by confocal microscopy. The expression of the MCR in the HEL cells was evident as a predicted band of 843 bp (234 amino acids) in electrophoresis of the PCR product obtained after total RNA had been reverse transcribed and then amplified using the primers 5'-AGGCTACCACAGTCTCCCTG-3' and 5'-GCAGTGTAAAATCTCCAGTC-3' (sense and antisense, respectively). The ENaC was similarly evident with the aid of the primers 5'-CTGCCmATG GATGATGGT-3' (sense) and 5'-GTTCAGCTCGAAGAAGA-3' (antisense) as a predicted band of 520 bp. In both cases, 100% identity was observed between the sequences of the PCR products compared to those from known human sources. The multiplication of the HEL cells was influenced by antagonists (RU 26752, ZK 91587) targeted for specificity to the MCR and this was selectively reversed by the natural hormone aldosterone. These steroids also provoked chromatin condensation in the HEL population. These permit new and novel possibilities to understand the pathobiology of human leukemia and to delineate sodium-water homeostasis in nonepithelial cells.
Leukemia 2000 Jun
PMID:Demonstration of the mineralocorticoid hormone receptor and action in human leukemic cell lines. 1086 75

Retrovirus Gag precursor (PrGag) proteins direct the assembly of roughly spherical immature virus particles, while after proteolytic processing events, the Gag capsid (CA) and nucleocapsid (NC) domains condense on viral RNAs to form mature retrovirus core structures. To investigate the process of retroviral morphogenesis, we examined the properties of histidine-tagged (His-tagged) Moloney murine leukemia (M-MuLV) capsid plus nucleocapsid (CANC) (His-MoCANC) proteins in vitro. The His-MoCANC proteins bound RNA, possessed nucleic acid-annealing activities, and assembled into strand, circle (or sphere), and tube forms in the presence of RNA. Image analysis of electron micrographs revealed that tubes were formed by cage-like lattices of CANC proteins surrounding at least two different types of protein-free cage holes. By virtue of a His tag association with nickel-chelating lipids, His-MoCANC proteins also assembled into planar sheets on lipid monolayers, mimicking the membrane-associated immature PrGag protein forms. Membrane-bound His-MoCANC proteins organized into two-dimensional (2D) cage-like lattices that were closely related to the tube forms, and in the presence of both nickel-chelating lipids and RNAs, 2D lattice forms appeared similar to lattices assembled in the absence of RNA. Our observations are consistent with a M-MuLV morphogenesis model in which proteolytic processing of membrane-bound Gag proteins permits CA and NC domains to rearrange from an immature spherical structure to a condensed mature form while maintaining local protein-protein contacts.
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PMID:Assembly of retrovirus capsid-nucleocapsid proteins in the presence of membranes or RNA. 1090 96

Because IL-3-dependent multipotential FDCP-Mix cells expressing human colony-stimulating factor-1 (CSF-1) receptor did not proliferate in response to soluble CSF-1, we investigated whether their proliferation would be induced in co-culture with adherent cells expressing the membrane form of CSF-1 (MemCSF-1). FDCP-Mix cells with high CSF-1R expression (NAF21 cells) were placed on stromal MS-5 cells or STO fibroblasts expressing MemCSF-1 (2M-1 cells and STO-M2 cells, respectively), in absence of IL-3. NAF21 cells bound significantly to 2M-1 cells as compared to control FDCP-Mix cells. Adhesion of NAF21 cells was inhibited by anti-huCSF-1 antibodies, as well as anti-huCSF-1R antibodies. Interestingly, NAF21 cells proliferated on both 2M-1 and STO-M2 cells but with very different kinetics. Moreover, NAF21 cell proliferation was also supported by glutaraldehyde-fixed 2M-1 cells or highly concentrated MS-5 cell culture supernatant, but not by CSF-1 coated on culture dishes. These results strongly suggest that MemCSF-1/CSF-1R interaction mediates a specific adhesion of NAF21 cells to stromal cells and allows stimulation of hematopoietic cells by stromal cell-derived factors expressed in a membrane-bound form or concentrated within the extracellular matrix. Thus, cytokine receptors deficient in mitogenic signalling may nevertheless have a regulatory role in hematopoietic progenitor cell proliferation by acting as adhesion molecules.
Leukemia 2000 Aug
PMID:Role of the membrane form of human colony-stimulating factor-1 (CSF-1) in proliferation of multipotent hematopoietic FDCP-mix cells expressing human CSF-1 receptor. 1094 43

We have used a method for the two-dimensional crystallization of retroviral structural proteins to obtain a three-dimensional structure of negatively stained, membrane-bound, histidine-tagged Moloney murine leukemia virus (M-MuLV) capsid protein (his-MoCA) arrays. Tilted and untilted micrographs from crystals formed by purified his-MoCA proteins incubated beneath lipid monolayers containing nickel-chelating lipids were used in 3D reconstructions. The 2D crystals had unit cell dimensions of a=72.6 A, b=72.5 A and gamma=119.5 degrees, but appeared to have no intrinsic symmetry (p1) in 3D, in contrast to the trigonal or hexagonal appearance of their 2D projections. Membrane-bound his-MoCA proteins showed a strand-like organization, apparently with dimer building blocks. Membrane-proximal regions, or putative N-terminal domains (NTDs), dimerized with different partners than the membrane-distal putative C-terminal domains (CTDs). Evidence also suggests that CTDs can adopt alternate orientations relative to their NTDs, forming interstrand connections. Our results are consistent with helical-spiral models for retrovirus particle assembly, but are not easily reconcilable with icosahedral models.
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PMID:Three-dimensional organization of retroviral capsid proteins on a lipid monolayer. 1096 65

Since the early 1970s, multiple drug resistance (MDR) has been known to exist in cancer cells and is thought to be attributable to a membrane-bound, energy-dependent pump protein (P-glycoprotein [P-gp]) capable of extruding various related and unrelated chemotherapeutic drugs. P-gp is coded for by the MDR1 gene, which in the human genome is located on the long arm of chromosome 7 (7q21-31). At the cellular level, the function of P-gp has been extensively investigated in human cancer. Although innumerable reports have been published in which P-gp has been shown to confer MDR to malignant (including leukemia) cells, so far, large-scale studies in the clinical setting have not convincingly proven that MDR1 plays a major role in clinical drug resistance when the influence of other known prognostic factors in human leukemia are taken into account. At present, results from phase 3 clinical trials evaluating the efficiency of inhibiting (or reversing) the function of P-gp in hematologic malignancies are eagerly awaited. Moreover, the horizon of cellular drug resistance in human cancer has during recent years widened dramatically. Thus, an array of different molecules and mechanisms by which resistant cells can escape the cytotoxic effect of anticancer drugs has now been identified. These molecules and mechanisms include apoptosis-related proteins. In this article, we review the different methods for determining MDR and, in particular, methods for determining P-gp/MDR1, with special reference to their potential importance for therapeutic strategies in human acute leukemia.
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PMID:Biology of multiple drug resistance in acute leukemia. 1118 84

PNH is a disorder of the pluripotent stem cells resulting in a deficient expression of membrane-bound GPI-anchored proteins in different cell types. Several flow cytometric approaches are designed to detect this antigen deficiency. But they all require drawing and testing of normal samples as control. Therefore, in the present study two flow cytometric assays for the detection of CD55 and CD59 deficiency in erythrocytes (REDQUANT CD55/CD59) and granulocytes (CELLQUANT CD55/CD59) are proposed. Precalibrated beads are used to define the cut off between normal and deficient cell populations. The specificity of the tests has been evaluated in healthy blood donors (n=52) resulting in a clear and reproducible cut off (3%) for the normal percentage of GPI-deficient cells. This cut off has been confirmed in leukaemia and lymphoma patients not suspected for developing PNH. The sensitivity has been tested in patients suffering from known PNH (n=23). Both tests performed in combination allowed a reliable detection of PNH in all patients showing antigen deficiencies in both cell types in most patients (20/23). In contrast, the PNH clones in the investigated patients with MDS (4/19) or AA (4/22) were present in granulocytes or erythrocytes, only. This underlines the necessity of analysing erythrocytes as well as granulocytes. Preliminary data regarding a possible correlation between disease activity and percentage of antigen-deficient cells lead to the assumption that haemolytic crises can only be determined on granulocytes whereas deficient erythrocytes disappeared due to complement-mediated lysis of the PNH clone. In conclusion, the combination of the test kits enables the differential diagnosis of PNH clones in a standardized, simple and rapid approach which may have therapeutic consequences.
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PMID:A standardized flow cytometric method for screening paroxysmal nocturnal haemoglobinuria (PNH) measuring CD55 and CD59 expression on erythrocytes and granulocytes. 1148 46

Hypercalcemia is one of the most frequent and serious complications in patients with adult T-cell leukemia (ATL) and is due to marked bone resorption by accumulation of osteoclasts (OCLs). Although several cytokines such as interleukin 1 and parathyroid hormone-related protein are thought to be involved in the development of high serum Ca(++) levels, its precise underlying mechanism remains unknown. This study analyzed the expression of various genes that are thought to regulate serum Ca(++) levels in ATL and showed that the overexpression of the receptor activator of nuclear factor kappaB (RANK) ligand gene correlated with hypercalcemia. ATL cells from patients with hypercalcemia, which highly expressed the transcripts of the RANK ligand (RANKL) gene, induced the differentiation of human hematopoietic precursor cells (HPCs) into OCLs in vitro in the presence of macrophage colony-stimulating factor (M-CSF). In contrast, ATL cells from patients without hypercalcemia did not induce such differentiation, suggesting that the induction of the differentiation correlated with the expression of the RANKL gene in ATL cells. Cell differentiation was suppressed by osteoprotegerin/Fc, an inhibitor of RANKL, indicating that such differentiation occurred through the RANK-RANKL pathway. In addition, direct contact between ATL cells and HPCs was essential for the differentiation, suggesting that not the soluble form but membrane-bound RANKL played a role in this process. These results strongly suggested that ATL cells induce the differentiation of HPCs to OCLs through RANKL expressed on their surface, in cooperation with M-CSF, and ultimately cause hypercalcemia.
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PMID:Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappaB ligand on adult T-cell leukemia cells. 1178 Dec 48

Macrophage colony-stimulating factor (M-CSF) plays important roles in hematopoietic and immunologic systems. Some isoforms or mutations have been demonstrated including membrane-bound and cellular M-CSF, which associated with some leukemia, lymphoma and other solid tumors. We previously reported that the M-CSF-like membrane-associated factor (MAF-J6-1) and its receptor was found from human leukemic cell line J6-1. In this report, the cDNA of MAF-J6-1 and its receptor were cloned. The cDNA sequence of MAF-J6-1 shows a 768bp open reading frame (ORF) with 99.2% homology to m-M-CSF, but six site mutations, including two synonymous mutations and four missense mutations. The cDNA of MAF-J6-1-R has a 2916bp ORF shared 99.6% homology with M-CSF-R, but 13 site mutations, including six synonymous mutations and seven missense mutations. At the same time, a 1662bp mutant s-M-CSF cDNA, which has 10 site mutations including three synonymous mutations and seven missense mutations, was cloned from J6-1 cells. The cDNAs of MAF-J6-1 and MAF-J6-1-R were inserted into a mammalian expression plasmid pTARGET and were expressed in COS-7 cells that demonstrated by their specific MAb. COS-7 cells transfected with MAF-J6-1-R show obvious protein tyrosine kinase (PTK) activity. Our present work shows that MAF-J6-1 and its receptor are mutations of M-CSF and its receptor.
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PMID:Clone and expression of mutant M-CSF and its receptor from human leukemic cell line J6-1. 1183 81

We constructed a soluble minimal receptor-Ig chimera in which the two extracellular domains of human Fcepsilonhain (D1 and D2) were fused to the dimerizing C-terminal domain of human IgG1 heavy chain (gamma1-CH3). The protein was expressed and actively secreted by Chinese hamster ovary (CHO) cells as a fully glycosylated soluble dimeric protein. It showed efficient binding both to human membrane-bound IgE isoforms and to the two secretory IgE isoforms. Moreover, the dimeric receptor binds IgE with the expected 1:2 stoichiometry. The receptor-Ig chimera, in 2-fold molar excess, inhibited engagement of secretory IgE to rat basophilic leukemia cells expressing the human alphabetagamma receptor. Full self-nature and inability to bind Fcgamma receptors make this protein an attractive candidate for clinical applications and a novel biotechnological tool for atopic allergy research.
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PMID:A minimal receptor-Ig chimera of human FcepsilonRI alpha-chain efficiently binds secretory and membrane IgE. 1184 38


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