Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

25-Hydroxycholecalciferol (25-OHD3) is converted to 8 alpha,25-dihydroxy-3-oxoneocholecalciferol [8,25-(OH)2-3-oxoneo-D3] by liver microsomes, alveolar macrophages and myeloid leukemia cells. The characteristics of this reaction in liver microsomes have been determined. Omission of an NADPH-generating system or NADH resulted in a greater than 75% reduction in the production of 8,25-(OH)2-3-oxoneo-D3. In the absence of the cytosolic fraction, 25-OHD3 was converted to products that comigrated with 8,25-(OH)2-3-oxoneo-D3 on a silica column developed with hexane-isopropanol, thereby preventing quantitation. Production of 8,25-(OH)2-3-oxoneo-D3 was unaffected by EDTA and was stimulated by N,N'-diphenyl-p-phenylenediamine. Both progesterone and pregnenolone inhibited production of 8,25-(OH)2-3-oxoneo-D3; inhibition by progesterone was greater than that by pregnenolone. 8,25-(OH)2-3-Oxoneo-D3 did not bind the thymus receptor for 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] at concentrations 10-fold higher than that of 1,25-(OH)2D3. The lack of affinity of 8,25-(OH)2-3-oxoneo-D3 for the 1,25-(OH)2D3 receptor suggests that this metabolite is a degradative product of 25-OHD3, which might be produced when 25-OHD3 concentrations in the liver are excessive. Synthesis of this metabolite in the liver may be catalyzed by enzymes that also metabolize other steroids.
J Steroid Biochem Mol Biol 1991 Jun
PMID:Synthesis and function of 8 alpha,25-dihydroxy-3-oxoneocholecalciferol in liver. 206 90

The jun-B gene is a member of the jun family of immediate early response genes that regulate cellular responses to growth factors. The present studies have examined the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on jun-B expression in human KG-1 myeloid leukemia cells. The results demonstrate that ara-C increases jun-B mRNA levels. The level of jun-B transcripts was maximal after 12 hr of exposure to 10(-5) M ara-C and persisted through 72 hr. Nuclear run-on assays demonstrated that ara-C treatment is associated with an increased rate of jun-B gene transcription. The results also demonstrate that ara-C-induced jun-B mRNA levels are regulated by a posttranscriptional mechanism. The level of jun-B transcripts in ara-C-treated cells was superinduced by inhibition of protein synthesis. Moreover, cycloheximide prolonged the half-life of ara-C-induced jun-B transcripts. These results, thus, demonstrate that ara-C induces expression of the jun-B gene in KG-1 cells and that this effect is mediated by transcriptional and posttranscriptional mechanisms.
Mol Pharmacol 1990 Oct
PMID:Regulation of jun-B gene expression by 1-beta-D-arabinofuranosyl-cytosine in human myeloid leukemia cells. 212 29

BXH-2 mice have the highest incidence of spontaneous retrovirally induced myeloid leukemia of any known inbred strain and, as such, represent a valuable model system for identifying cellular proto-oncogenes involved in myeloid disease. Chronic murine leukemia viruses often induce disease by insertional activation or mutation of cellular proto-oncogenes. These loci are identified as common viral integration sites in tumor DNAs. Here we report on the characterization of a novel common viral integration site in BXH-2 myeloid leukemias, designated Evi-2. Within the cluster of viral integration sites that define Evi-2, we identified a gene that has the potential for encoding a novel protein of 223 amino acids. This putative proto-oncogene possesses all of the structural features of a transmembrane protein. Within the transmembrane domain is a "leucine zipper," suggesting that Evi-2 is involved in either homopolymer or heteropolymer formation, which may play an important role in the normal functioning of Evi-2. Interestingly, the human homolog of Evi-2 has recently been shown to be tightly linked to the von Recklinghausen neurofibromatosis locus, suggesting a role for Evi-2 in human disease as well.
Mol Cell Biol 1990 Sep
PMID:Evi-2, a common integration site involved in murine myeloid leukemogenesis. 216 36

Transcription from the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) is inhibited in murine stem cells and induced during maturation of these cells. We have investigated whether alterations in the activity of this viral regulatory element also occur during differentiation of human myeloid leukemia cells. The Mo-MuLV LTR and the simian virus 40 (SV40) early promoter were introduced into HL-60 promyelocytes on Epstein-Barr virus-derived chloramphenicol acetyltransferase expression vectors. When these cells were induced to terminally differentiate, transcription from the Mo-MuLV LTR was induced approximately 10-fold. Expression from the SV40 promoter remained constant during differentiation of these cells. Replacing the SV40 transcriptional enhancer with the Mo-MuLV LTR transcriptional enhancer rendered the SV40 promoter inducible during differentiation. We conclude that sequences within the transcriptional enhancer of the Mo-MuLV LTR contain cis-acting elements responsible for induction of gene expression during differentiation of human myeloid cells.
Mol Cell Biol 1989 Aug
PMID:Induced expression from the Moloney murine leukemia virus long terminal repeat during differentiation of human myeloid cells is mediated through its transcriptional enhancer. 247 90

The effects of catalase treatment were studied in two in vitro passaged ascites tumour lines (ATP C+ and EAT) and in three in vitro established human myeloid leukemia cell lines (HL-60; KG-1; KG-1a) characterized by the arrest of cells at different stages of maturation. The results demonstrate that catalase treatment favoured proliferation in the in vitro passaged ascites tumour cells, but not in the in vitro established leukemia lines. Enzyme assays on five in vitro cell lines revealed that catalase was only present in HL-60. Although glutathione peroxidase activity was initially found in all five cell lines, it disappeared from two ascites tumour cells when they were transferred in culture. It is hypothesized that catalase treatment favours ascites tumour cell proliferation because it replaces glutathione peroxidase in eliminating H2O2.
Cell Mol Biol 1989
PMID:Antioxidant enzymes and proliferative activity of cell lines of different origin. 261 35

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.
Mol Cell Biol 1987 Dec
PMID:Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA. 348 35

A planimetric study of megakaryopoiesis in various chronic myeloproliferative diseases (CMPD) was performed and the results compared with those from controls and myelitis of rheumatic origin. Morphometric measurements included at least 200 megakaryocytes in each case observed in Giemsa-stained semithin sections of resin-embedded core biopsies. Twenty specimens were evaluated from the controls and inflammatory disorders and from each of the following CMPD: 1, chronic granulocytic leukaemia (CGL); 2, polycythaemia vera (P. vera); 3, chronic megakaryocytic-granulocytic myelosis without or with minimal increase in reticulin fibre content (CMGM); 4, myelofibrosis or osteomyelosclerosis (MF/OMS). Megakaryocytes were classified as follows: 1, normal megakaryocytes at all stages of maturation; 2, giant forms; 3, microforms; 4, intussusceptions; 5, a-nuclear cytoplasmic fragments; 6, naked nuclei or necrotic forms. The results of this study demonstrate obvious abnormalities of megakaryopoiesis in addition to the increase in absolute numbers of megakaryocytes per marrow area and their different sizes as reported earlier (Thiele et al. 1982). Aberrations are particularly conspicuous when pure granulocytic proliferation or neoplasia of CGL is compared with the so-called mixed cellularity of megakaryocytes and granulocytes in CMGM including MF/OMS. Abnormalities of the giant forms of megakaryocytes are especially evident and comprise irregular cellular and nuclear perimeters (as calculated by a modified shape factor) in the two latter entities (CMGM-MF/OMS). This remarkable feature is associated with a disorganization of nuclear development and/or a disproportionate nuclear-cytoplasmic ratio which has never been observed in CGL previously. In combination with this striking cellular anomaly, which is compatible with an extreme amoeboid shape of giant forms in CMGM and MF, intussuceptions and a-nuclear cytoplasmic fragments are frequently encountered. The final stage of megakaryopoiesis, i.e. naked nuclei, are increased in number in all CMPD, probably because of enhanced proliferation and platelet shedding. Naked nuclei are often small in CGL (as remnants of the frequent micromegakaryocytes) and large in P. vera and CMGM/MF (depending on the high incidence of giant megakaryocytes in these latter disorders).
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Abnormalities of megakaryocytes in myelitis and chronic myeloproliferative diseases. 613 85

Human myeloid leukemia cell lines ML-1, ML-2, ML-3, promyelocytic leukemia cell line HL-60 and histiocytic lymphoma cell line U-937 were induced to differentiate by 0.5-10 ng/ml (0.8-16 nM) 12-O-tetradecanoylphorbol-13-acetate (TPA). After 48-72 h of induction, changes of the morphology, cytochemistry and of the antigenic phenotype of induced and control cells were studied using a panel of monoclonal antibodies against granulocytic, monocytic, HLA-ABC and HLA-DR antigens in indirect immunofluorescence. Cells of the TPA-treated cultures acquired morphological, cytochemical and antigenic markers of monocytes/macrophages, as surface adherence, alpha-naphthyl acetate esterase (alpha-NE) and acid phosphatase activity and the expression of monocytic antigens detected with monoclonal antibodies 63D3, FMC 17, B 44.1, B 52.1 and anti-Mol. During differentiation in vitro induced by TPA, also loss of HLA-DR antigens and diminution of antigen of cell activation were detected with antibodies L 243 and 4F2. The expression of granulocytic antigens was only slightly diminished and the expression of HLA-ABC antigens was not changed by TPA-treatment. There were differences in the percentage of cells induced to differentiate among the lines of different origin and even among the lines ML-1, ML-2 and ML-3, established from a single patient with acute myeloid leukemia. After treatment of cultures with 5 ng/ml TPA for 72 h DNA synthesis was inhibited to 60-80%.
 ...
PMID:Differentiation of human myeloid leukemia cell lines induced by tumor-promoting phorbol ester (TPA). I. Changes of the morphology, cytochemistry and the surface differentiation antigens analyzed with monoclonal antibodies. 634 16

This review summarizes recent data concerning the immunogenicity and immunomodulatory properties of glycosphingolipids. Many murine monoclonal antibodies that react with glycosphingolipids have been described recently. Most of these antibodies have been elicited by immunization with tumor cells and they may also bind to glycoproteins that contain similar carbohydrate sequences. Immunization with a variety of tissues, murine teratocarcinomas, myeloid leukemia, and carcinomas of the human lung, colon and stomach, has elicited antibodies that react with the sugar sequence Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal----. The suppression of lymphocyte responses to mitogens and antigens by gangliosides in vitro has led to suggestions that these glycolipids possess immunodulatory properties in vivo. The in vitro studies were performed by incubating mononuclear cells with either dispersions of pure gangliosides or ganglioside-containing liposomes. In vivo gangliosides are found only in cell membranes or in lipoproteins, where they represent a small mole percent of total lipids, and there is little information about the transfer of gangliosides from lipoproteins to cells in vivo. A role for gangliosides as modulators of the immune response is an interesting possibility that is not supported by physiologically relevant data at present.
Mol Immunol 1984 Nov
PMID:A review of the immunogenic and immuno-modulatory properties of glycosphingolipids. 639 57

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-M0. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-M0, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-M0, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-1a. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1995 Sep
PMID:Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization. 749 41


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