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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of homoribopolymer-directed DNA synthesis by detergent-disrupted Moloney murine leukemia virus can be stimulated or inhibited by histone, depending on the ratio of histone to template. Of the fractions which can be separated from the whole histone, f1 causes both the greatest stimulation and the greatest inhibition. The effect of histone f1 is qualitatively similar whether the template is polyadenylate (poly A), polycytidylate, or polyuridylate, but the stimulation is greatest with poly A. The pattern of stimulation and inhibition differs, however, for a different polymerase; the DNA polymerase of Micrococcus luteus is inhibited by histone concentrations which stimulate the viral enzyme and stimulated by concentrations which inhibit the viral enzyme. For the viral enzyme, the optimum histone concentration is unaffected by changes in the virus or primer concentration; but it varies in proportion to the template concentration, suggesting that histone acts by combining stoichiometrically with the template. These data raise the possibility that a histone-like protein may participate in the synthesis of the provirus of RNA tumor viruses.
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PMID:Histones stimulate polyribonucleotide-directed polydeoxyribonucleotide synthesis by murine leukemia virus. 485 39

The organization and expression of human histone genes were examined in W138 normal human diploid fibroblasts, SV40 transformed W138 cells, A549 epithelial lung carcinoma cells, two adeno-carcinoma cell lines (LOVO and HT29) and three leukemia cell lines (HL60, KG1 and K562). Analysis of the restriction enzyme digests of total genomic DNAs by hybridization with a series of cloned human histone sequences indicated polymorphic organization of at least a subset of the moderately reiterated human histone genes in these cells. Quantitative and qualitative differences were also observed in the representation of histone mRNAs by Northern blot analysis using cloned human histone genes as hybridization probes. However, there was no apparent correlation between variations in the representation of transcripts from various copies of the histone genes, variations in histone gene organization, and the extent of tumor progression.
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PMID:Variations in the organization and expression of human histone genes in normal diploid and tumor cell lines. 620 Nov 32

Determination of levels and isozymic patterns of protein kinase activities was performed upon extracts from two human leukemia cell lines (K562 and HL-60) and blast cells from five untreated patients with acute myeloblastic leukemia and compared to activities from normal human peripheral blood granulocytes and bone marrow samples enriched for proliferative myeloid cells. The leukemic cells studied were found to have higher specific activities of cytosol cyclic adenosine 3':5'-monophosphate (cAMP)-independent casein kinase and lower activation by cAMP of their cytosol histone kinase compared to the normal myeloid cells studied. Diethylaminoethyl-cellulose chromatography revealed correspondingly higher amounts of cAMP-independent protein kinase isoenzymes (two casein kinase and one histone kinase peaks) in the leukemic cells, as well as altered ratios of the two cAMP-dependent isozymes. Casein phosphorylating activities extracted from the nuclei of the leukemic cell lines were also high compared to normal myeloid cells. Further purification and estimation of molecular weights of the isoenzymes present in leukemia were accomplished by gel filtration, using Sephacryl S-200. Resolution of the acute myeloblastic leukemia cell line nuclear casein kinase activity into two peaks was also thereby accomplished. The nuclear peaks eluted earlier than the corresponding cytoplasmic peaks; thus, the nuclear isoenzymes may not be identical to those from the cytoplasm. The increased protein kinase activity noted in such cells may be an important biochemical concomitant of transformation.
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PMID:Cyclic adenosine 3':5'-monophosphate-dependent and -independent protein kinase in acute myeloblastic leukemia. 626 62

Using [32P]histone as substrate, an assay for histone phosphate phosphatase was optimised for human polymorphonuclear leukocytes. Kinetic studies showed that the activity was optimal at pH 6.8, was stimulated by Mn2+ and Co2+, and inhibited by sodium sulphite and zinc chloride. The apparent Km of the enzyme for histone phosphate was 0.89 mumol/l. Neutrophils were homogenized in isotonic sucrose and, after low speed centrifugation, the supernatant was subjected to analytical subcellular fractionation. Gradient fractions were assayed for principal marker enzymes and for histone phosphate phosphatase. Histone phosphate phosphatase activity was shown to be solely located to the cytosol. No activity was detected in the alkaline phosphatase-containing granules. Neutrophils were isolated from the blood of control subjects, patients with chronic granulocytic leukaemia and women in the third trimester of pregnancy. The specific activity (milliunits/mg protein) of histone phosphate phosphatase was significantly reduced in patients with chronic granulocytic leukaemia compared to control values but this decrease was considerably less than that found for alkaline phosphatase. The possible implication of the reduced histone phosphatase activity in leukaemia neutrophils is discussed. There was no significant change in histone phosphate phosphatase in leucocytes from pregnant women. These results, together with the subcellular fractionation experiments and inhibitor studies, strongly indicate that histone phosphate phosphatase is not attributable to neutrophil alkaline phosphatase.
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PMID:Subcellular localisation and properties of histone phosphate phosphatase in human polymorphonuclear leukocytes: alterations in pregnancy and chronic granulocytic leukaemia and relationship to alkaline phosphatase. 693 12

Nucleolin and fibrillarin are two histone-like major proteins in the nucleolus that were found to be overexpressed in proliferating cells. Using specific antibodies to either nucleolin or fibrillarin flow cytometric, measurements were carried out to demonstrate quantitative changes of these proteins during lymphocyte mitogenic activation and differentiation of HL-60 promyelocytic leukaemia cells. The expression of nucleolin increased during lymphocyte stimulation and decreased slowly but constantly in the course of differentiation of HL-60 cells. Expression of fibrillarin reached a maximum in the first cell cycle and then dropped to a basic level in stimulated lymphocytes. Compared to nucleolin, the level of fibrillarin decreased more rapidly and more extensively in differentiating HL-60 cells. The data support other observations that nucleolin is a stabile structural protein at the ribosomal genes while fibrillarin may have a more specific functional role in nucleologenesis and ribosome production.
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PMID:Nucleolin and fibrillarin expression in stimulated lymphocytes and differentiating HL-60 cells. A flow cytometric assay. 762 87

The levels and fractional composition of nuclear proteins of human leukocytes (histones, total non-histone proteins and HMG-proteins) have been studied in healthy subjects and cases of leukemia. It has been shown that the levels of histones and total non-histone proteins in normal myeloid cells are, on the average, 1.5 times those in lymphoid cells. Leukemia has been shown to involve elevated concentrations of high-molecular components in the histone and HMG-protein fraction of white blood cells as well as a slight decrease in both high- and low-molecular components in the fraction of total non-histone proteins. This points to disturbances in the epigenomic regulation of the genome involved in leukemia.
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PMID:[Nuclear proteins of human leukocytes in health and in chronic leukemias]. 782 98

Cloning and sequence analysis of about 2 kb of the 5' flanking region of the human H1 zero histone gene reveals several potential regulatory elements upstream of the transcribed portion of this gene. Transfection studies using the chloramphenicol acetyl transferase (CAT) gene as a reporter gene with a series of promoter deletions revealed that the expression of the H1 zero gene may depend on a complex interplay of several transcription factors, including members of the retinoic acid and/or thyroid-hormone-receptor superfamily, at the 5' flanking region of the H1 zero gene. CAT assays demonstrate varied patterns of expression and regulation in different human tumor-cell lines. The leukemia cell line HL60 does not express H1 zero mRNA and shows no CAT activity. HeLa cells strongly express the CAT gene under the control of the H1 zero promoter. Under the same conditions, HepG2 cells also transcribe the CAT gene, although at a lower rate than HeLa cells. Using different promoter-deletion clones, the CAT activity differs in HepG2 and HeLa cells in the very distal promoter region. In both cell lines, the CAT activity decreases several fold when the region between nucleotides -450 and -600 upstream of the mRNA start site is deleted. It also decreases when just the proximal portion but not the distal promoter region is deleted. In summary, the regulatory patterns of these three cell lines differ, indicating a cell-type-specific regulation of the human H1 zero-histone-gene expression.
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PMID:Differential regulation of the human H1 zero-histone-gene transcription in human tumor-cell lines. 822 73

Peptide palindromes are invariably found in all proteins, and long palindromes exceeding 10 residues in length are not rare. They are particularly abundant in DNA-binding proteins such as H1 histone. When a complementary strand of the coding sequence is translatable being free of a chain terminator, a complementary protein encode by it becomes equally abundant in peptide palindromes. The simultaneous musical transformation of both strands of mouse H1 histone variety-1 DNA enable us to appreciate the symmetrical beauty of successive palindromes appearing in both H1 histone and its complementary protein.
Leukemia 1993 Aug
PMID:A song in praise of peptide palindromes. 836 Dec 24

The relationship between chromatin structure and endonuclease sensitivity was investigated. The cells used in this study were a) human myelogenous leukemic cell lines (HL-60, ML-I, U-937, THP-I) (Group I), which produced internucleosomal DNA cleavage, and b) human T-cell leukemia (MOLT-4), erythroleukemia (K562), glioblastoma (T98G, U87MG) and glioma (KG-1-C) cell lines (Group II), which produced no internucleosomal DNA cleavage, upon treatment with various apoptosis-inducing agents. When the nuclei, isolated from these cells were digested with micrococcal nuclease, chromatin DNA was cleaved into oligonucleosomal units. Although sensitivity to micrococcal nuclease considerably differed from cell to cell, Group I cells were generally more sensitive to micrococcal nuclease digestion than Group II cells. Similar sensitivity to DNase I was observed in both groups of cells. Acid-urea polyacrylamide gel electrophoresis of histone fractions from control and apoptosing HL-60 cells (induced either by hydrogen peroxide or UV irradiation) revealed no significant change in the relative composition of five major histones, indicating the absence of selective degradation of histone HI, but rather the nonspecific degradation of many nuclear proteins. These data suggest a difference in a chromatin structure between Group I and II cells, which might result in the selective production of internucleosomal DNA cleavage only in Group I cells.
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PMID:Chromatin structure and endonuclease sensitivity in human leukemic cell lines. 870 41

Previous studies have demonstrated that the active metabolite of leflunomide, A77 1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], is capable of inhibiting the activities of tyrosine kinases and dihydroorotate dehydrogenase (DHO-DHase). In the present study, we define the relative contribution of these activities to the ability of A77 1726 to inhibit proliferation of the murine leukemia cell line LSTRA. A77 1726 inhibited LSTRA cell growth and proliferation (IC50 = 10-30 microM); this inhibition, however, could be reversed by the addition of exogenous uridine, suggesting that the anti-proliferative activity of A77 1726 may be due to inhibition of de novo pyrimidine nucleotide synthesis. Quantitation of nucleotide levels revealed that A77 1726, at an IC50 of about 10 microM, selectively inhibited pyrimidine nucleotide but not purine nucleotide synthesis. In vitro enzyme assays confirmed that A77 1726 directly inhibited the activity of DHO-DHase, the fourth enzyme in the de novo pathway of pyrimidine nucleotide synthesis (IC50 = 220 nM). LSTRA cells overexpress p56lck and have elevated levels of tyrosine phosphorylated intracellular proteins. A77 1726 reduced the intracellular levels of tyrosine phosphorylated proteins with relatively high IC50 values ranging from 50 to 100 microM. A77 1726 also inhibited p56lck activity in LSTRA membrane preparation and immunoprecipitates; the IC50 values for inhibition of immunoprecipitated p56lck autophosphorylation and exogenous substrate histone 2B were 80 and 40 microM, respectively. The anti-tyrosine phosphorylation activity of A77 1726 was not affected by uridine. These studies therefore demonstrate the two activities of A77 1726: inhibition of pyrimidine nucleotide synthesis and interference with tyrosine phosphorylation.
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PMID:Two activities of the immunosuppressive metabolite of leflunomide, A77 1726. Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylation. 875 24


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