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)

The knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil-related proteins, i.e. mast cell tryptase, mast cell carboxypeptidase A, high-affinity immunoglobulin (IgE) receptor alpha and gamma chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/-macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distinguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil-specific markers eosinophil cationic protein, eosinophil-derived neurotoxin or eosinophil peroxidase. We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein. Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil-specific marker(s).
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PMID:Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. 163 3

The activity of asparagine synthetase decreased almost 50% during dexamethasone-induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also declined significantly during differentiation of the human myelogenous leukemic cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or retinoic acid. The decline of asparagine synthetase activity closely paralleled the expression of various maturation markers, but could also be induced by serum starvation. These results suggest that asparagine synthetase or L-asparagine has some biological function in growth regulation of these leukemia cell lines.
Leukemia 1990 Oct
PMID:Decrease in asparagine synthetase activity during cell differentiation of mouse and human leukemia cell lines. 197 72

Glucocorticoids can mediate the destruction of thymocytes and T cell-derived leukemia cells through a mechanism known as apoptosis. The characteristic feature of apoptosis is fragmentation of DNA at internucleosomal linkers through the activity of a specific endonuclease. In this study, an attempt was made to compare dexamethasone-induced apoptosis in two T cell-derived human leukemia lines (CEM-C1 and CEM-C7) to the cell killing brought about by selected cytotoxic agents. In the CEM-C7 cell line (dexamethasone-sensitive), apoptosis was induced not only by dexamethasone but by actinomycin D, cycloheximide, and 25-OH cholesterol. In the CEM-C1 cell line (dexamethasone-resistant) cycloheximide, 25-OH cholesterol, or cell starvation could induce apoptosis. It appears that in leukemic cells apoptosis may be induced by a variety of unrelated toxic agents and is not limited to glucocorticoids.
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PMID:Apoptosis: mode of cell death induced in T cell leukemia lines by dexamethasone and other agents. 200 65

L-Histidinol, an analogue of the amino acid L-histidine, has been reported to be able to increase the specificity of 5-fluorouracil (FUra), through both protection of normal tissues at risk and potentiation of leukemic cell killing. It is postulated that this occurs through prevention of the entry of normal cells into the cell cycle through protein deficiency, while allowing malignant cells, permissive for protein starvation, to continue to cycle, thus maintaining sensitivity for cycle specific anticancer agents. Reported in this paper is the confirmation of these L-histidinol-FUra effects. However, a modification was made by which more L-histidinol could be given and more consistent protection of whole animals demonstrated. Further, an optimal schedule of L-histidinol was defined in which FUra preceded L-histidinol infusion. Finally, the specificity and proliferation dependence of this schedule was evaluated on colony forming units-spleen in resting and proliferating state, colony forming units-granulocyte-macrophage, and L1210 leukemia. This demonstrates that the FUra/L-histidinol combination indeed protects only normal cells but that the postulated proliferation dependence is absent, indicating an alternate biological mechanism.
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PMID:Specificity, schedule, and proliferation dependence of infused L-histidinol after 5-fluorouracil in mice. 334 20

The production of Moloney murine leukaemia virus from chronically infected cells was inhibited after starvation of glutamine. While the rate of synthesis of the precursor of the core proteins, Pr65gag, was not affected in the starved cells, its proteolytic processing was blocked. Pulse-chase experiments indicated that glutamine was required during the synthesis of Pr65gag to facilitate its subsequent processing. In addition, the synthesis of Pr200gag-pol, the precursor of the protease, reverse transcriptase and endonuclease, was inhibited in the glutamine-starved cells. Starvation for other essential amino acids such as tyrosine and isoleucine affected neither the synthesis nor the processing of the virus proteins. These results suggest that the readthrough mechanism which enables synthesis of the Pr200gag-pol polyprotein is modulated in the chronically infected cells by glutamine levels. Since the viral protease is part of the pol gene, its synthesis may be inhibited in the glutamine-starved cells and Pr65gag is therefore not processed.
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PMID:Glutamine starvation of murine leukaemia virus-infected cells inhibits the readthrough of the gag-pol genes and proteolytic processing of the gag polyprotein. 348 14

The toxicity and metabolism of a thymidine analogue, 5-hydroxymethyl-2'-deoxyuridine (5HmdUrd) were studied with human leukemia cells (HL-60) and with human platelets. 3 X 10(-5) M 5HmdUrd caused a 50% inhibition in the proliferation of HL-60 cells. The compound was hydrolyzed to 5-hydroxymethyluracil (5HmUra) by the enzyme thymidine phosphorylase (EC 2.4.2.4) present in leukemia cells; this catabolic product was non-toxic. The catabolism of 5HmdUrd by human platelet thymidine phosphorylase could be inhibited by 6-aminothymine. The toxicity of 5HmdUrd was effectively reversed by deoxycytidine and 5HmdUrd increased the incorporation of deoxycytidine into dCTP and DNA several fold. The two latter phenomena are explicable in terms of a feedback action to ribonucleotide reductase, resulting in deoxycytidylate starvation, which is a known effect of excess thymidine. We report here also our preliminary observations that 5HmdUrd is active against mouse leukemia in vivo.
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PMID:In vitro and in vivo studies of a promising antileukemic thymidine analogue, 5-hydroxymethyl-2' deoxyuridine. 379 Jan 49

To investigate the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) at high doses as applied in human acute leukemia, the cytotoxic effect of high-dose ara-C was studied in L1210 leukemia cells grown in tissue culture or as tumors in syngeneic mice. Exponentially growing cells displayed the expected S-phase specificity and dose saturation properties of drug action. In contrast, in stationary cultures, progressively more cells were killed by increasing the concentration of the drug. Moreover, the fraction of cells killed at high doses exceeded by 2- to 3-fold the number of cells in drug-sensitive S phase detectable by flow cytometry or [3H]thymidine radioautography. To identify these apparent non-S targets of ara-C at high doses, L1210 cells were separated according to cell cycle position by velocity sedimentation at unit gravity. Large fractions of cells, accumulating at the G1-S boundary by nutrient starvation, were detected in stationary tissue culture cells as well as in ascites or solid tumor cells. The cells located in this cell cycle compartment (termed S1 cells) were sensitive to the cytotoxic effect of high-dose ara-C. The putative presence of similar S1 fractions in advanced human acute nonlymphocytic leukemia may explain in part the clinical efficacy of a high-dose application of the drug.
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PMID:S1-phase cells of the leukemic cell cycle sensitive to 1-beta-D-arabinofuranosylcytosine at a high-dose level. 400 48

In a previous report we demonstrated in mouse lymphoma (S-49) cells that DNA synthesis inhibition resulting from guanine starvation is associated with GTP rather than dGTP depletion. Since several effective anticancer drugs act via guanine depletion, it is important to test whether critical GTP depletion is unique to S-49 cells or also occurs in other cell lines. Mycophenolic acid-induced guanine starvation caused a drastic DNA synthesis inhibition in the human lymphoblastic T leukemia (CEM) and the mouse B leukemia (L1210) cell lines, which was again associated with GTP depletion rather than dGTP depletion. These results suggest that GTP depletion represents a common target of purine antimetabolites in mammalian cells.
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PMID:Guanine ribonucleotide depletion in mammalian cells. A target of purine antimetabolites. 657 81

The human leukemia K562 cell line can be induced by 20 micro M hemin to reversibly accumulate embryonic and fetal hemoglobins without any change in the rate of cell division. When we reduced the rate of cell division by glutamine starvation or addition of hydroxyurea, the cells increased by tenfold the basal hemoglobin level of 0.3-0.5 pg Hb/cell. The combined effects of hemin and inhibitors of cell division permitted K562 cells to attain levels of hemoglobin (26-34 pg Hb/cell) close to that found in normal red cells. This superinduction was reversible and cells could be recycled indefinitely. Furthermore, electrofocusing experiments show that the three primary hemoglobin species produced by these cells (Hb Gower 1, Hb Portland, and fetal Hb), were induced, or reinduced, synchronously by inhibitors of cell division but asynchronously by hemin. Differing effects of hemin and inhibitors of cell division were observed in the absence of irreversible differentiation and suggest different molecular mechanisms controlling globin gene expression.
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PMID:Inhibitors of cell division reversibly modify hemoglobin concentration in human erythroleukemia K562 cells. 694 49

The IGF regulatory system has been shown to mediate mitogenic effects during normal growth and tumor proliferation. The bioavailability of both IGF-I and IGF-II is regulated by at least six specific IGF binding proteins (IGFBPs). Whereas IGFBP-3 is the main IGFBP postnatally, IGFBP-2 is the predominant IGFBP during fetal life. In addition, IGFBP-2 is expressed in a range of tumor cell lines. In order to investigate the IGF regulatory pathway in malignancies we analyzed by RIA serum samples of 49 children with leukemia, Non-Hodgkins' Lymphoma (NHL) or solid tumors at the time of diagnosis. Serum concentrations of IGF-I (mean/range: -2.4/0.3 to -9.9 SDS), IGF-II (-2.5/0.2 to -5.6 SDS) and IGFBP-3 (-1.3/2.2 to -6.8 SDS) were significantly decreased, but IGFBP-2 (3.2/-0.9 to 8.6 SDS) was elevated. Both absolute as well as SDS values of IGF-I, -II and the sum of IGF-I and IGF-II (r = -0.49, p < 0.01) were inversely correlated with IGFBP-2. Serum levels of the growth factors IGF-I and IGF-II were significantly decreased in different types of malignancies to concentrations usually seen only in patients with growth hormone deficiency or during starvation. However, the elevated levels of IGFBP-2 in 70% of our patients exceeded by far those in growth hormone deficiency. Furthermore, in this study we could demonstrate that serum levels of IGF-I and IGF-II were inversely correlated to IGFBP-2 independent on the type of malignancy, indicating a common regulatory mechanism of the IGF signaling pathway in these diseases.
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PMID:[Serum concentrations of insulin-like growth factors (IGF)-I and IGF-II and IGF binding proteins (IGFBP)-2 and IGFBP-3 in 49 children with ALL, NHL or solid tumors]. 756 58


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