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)

Constant intracellular concentrations of both adenosine 3',5'-cyclic-monophosphate (cyclic AMP) and guanosine 3',5'-cyclic-monophosphate (cyclic GMP) were obtained when leukemia L1210 cells were cultivated under steady-state conditions in the chemostat. In this sensitive and controlled system addition of mouse interferon resulted in a rapid (5-10 min) increase in the intracellular concentration of cyclic GMP, which preceded by several hours an increase in the intracellular concentration of cyclic AMP. In contrast to the effect of interferon, addition of prostaglandin E1 induced a rapid increase in the intracellular concentration of cyclic AMP without markedly affecting the intracellular concentration of cyclic GMP. It is suggested that the rapid effect of interferon on cyclic GMP plays a role in mediating some of the effects of interferon on cells.
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PMID:Effect of interferon on concentrations of cyclic nucleotides in cultured cells. 22 87

Prostaglandins E1, E2, and F2alpha (PGE1, PGE2, and PGF2alpha) were shown to inhibit the growth of mouse leukaemia lymphoblasts L5178Y in culture. The effects of PGE1 and PGE2 were greater than that of PGF2alpha. PGE1 and PGE2, at the concentration of 100 mug per ml showed significant inhibitory effects on the rates of incorporation of tritiated thymidine, uridine and leucine. At concentrations of 50 and 25 mug per ml, there was significant inhibition of thymidine and uridine incorporation, but not of leucine, PGF2alpha showed significant inhibition of thymidine and uridine incorporation but not leucine incorporation, in all 3 concentrations studied (100, 50, and 25 mug/ml). The ability of the cells to form colonies in soft agar was significantly inhibited by PGE1 and PGE2 at concentrations as low as 1-8 mug/ml. For F2alpha, however, a concentration as high as 56mug/ml was required to show inhibitory effect, but at 1-8 mug/ml it was found to be stimulatory.
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PMID:Effects of prostaglandins E1, E2, and F2alpha on the growth of leukaemia cells in culture. 124 20

smg p21A and -B (smg p21s) are ras p21-like small GTP-binding proteins (G proteins) with the same putative effector domain as ras p21s. Both smg p21A mRNA and smg p21B mRNA were detected in CMK, a human megakaryocytic leukemia cell line, and their levels were markedly elevated by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which caused the differentiation of this cell line into more mature megakaryocytes. The smg p21 protein molecules also increased during the TPA-induced differentiation of CMK cells. The mRNA level of glycoprotein IIb (GPIIb), a typical marker of the megakaryocytes, was increased by this treatment, but the time course of the increase in the smg p21 mRNA levels as more rapid than that of the increase in the GPIIb mRNA level. Ha-ras p21 mRNA was undetectable, but both Ki- and N-ras p21 mRNAs were detected in CMK cells and their levels were also increased during TPA-induced differentiation of CMK cells, although to a lesser extent than those of smg p21 mRNAs. Protein kinase C inhibitors inhibited the basal and TPA-induced smg p21A mRNA level, but cyclic AMP-elevating prostaglandin E1 or Ca(2+)-mobilizing ionomycin did not inhibit them. Cycloheximide enhanced the basal and TPA-induced smg p21A mRNA levels. Actinomycin D blocked the TPA-induced smg p21A mRNA levels, but showed no detectable effect on the elevated smg p21A mRNA level which was induced by pretreatment with TPA. A dramatic increase in the smg p21 mRNA levels was also observed in other leukemia cell lines during TPA-induced differentiation. These results suggest that TPA stimulated expression of the smg p21A gene, presumably through the action of protein kinase C at the transcriptional level rather than at the post-transcriptional level, in hematopoietic leukemia cells.
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PMID:Induction of smg p21/rap1A p21/krev-1 p21 gene expression during phorbol ester-induced differentiation of a human megakaryocytic leukemia cell line. 154 53

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.
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PMID:Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line. 165 Mar 88

The effects of combinations of interferons (IFNs) and cAMP-inducing agents on the induction of differentiation of human monocytic leukemia U-937 cells were examined. IFN-gamma induced nitro blue tetrazolium (NBT) reducing activity of U-937 cells in a dose-dependent manner, while cAMP-inducing agents such as cholera toxin, prostaglandin E1, forskolin, and isoproterenol only marginally induced NBT reducing activity. However, they all synergistically increased IFN-gamma induction of NBT reducing activity. Cholera toxin was the most potent of the cAMP-inducing agents. Combination effects of IFN-gamma and cholera toxin on other differentiation-associated markers of alpha-naphthyl acetate esterase activity, morphological maturation, Fc receptors, and surface phenotype were also observed. IFN-alpha and -beta, either alone or in combination with cAMP-inducing agents, did not induce NBT reducing activity. IFN-gamma and cholera toxin also synergistically induced differentiation-associated markers in another human monocytic leukemia cell line, THP-1, and a human myeloblastic leukemia cell line, ML-1. These results suggest that cAMP/A-kinase may be an important but insufficient signal for the maturation process of myelogenous leukemia cells.
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PMID:Enhancement of interferon-gamma-induced differentiation of human monoblastic leukemia U-937 cells by cAMP-inducing agents. 170 96

MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.
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PMID:Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s. 171 95

Prostaglandin E1 (PGE1) was used to prevent veno-occlusive disease (VOD) of the liver after allogeneic bone marrow transplantation (BMT) for leukaemia. It was given in continuous i.v. infusion from day--8 to day 30 after BMT at a dose of 0.3 micrograms/kg/h. The patients were studied according to the risk factors for VOD: diagnosis, intensification of the conditioning and previous liver abnormalities. The diagnosis of VOD was made on at least two of the following factors: weight gain, hepatomegaly, jaundice, ascitis, pain of the right upper quadrant, increased platelet consumption. 109 patients were studied, 50 were treated by PGE1 and 59 did not receive it. The actuarial incidence of VOD was 12.2% in the PGE1 group and 25.5% in the non PGE1 group (P = 0.05). In acute leukaemia, the incidence was 39.1% in the non-treated group and 12.8% in the PGE1 treated group (P = 0.02). Patients with previous hepatitis had an incidence of 62.5% in the non treated group and 15.5% in the treated group (P = 0.05). A positive cytomegalovirus (CMV) serology seemed to increase the risk of VOD: the incidence of VOD was 31.4% in non-treated patients and 22% in PGE1 treated patients. The multivariate analysis of the risk factors for VOD shows that unfavourable factors were: recipient positive CMV serology (P = 0.06), hepatic disease prior to transplant (P = 0.02) and the absence of PGE1 treatment (P = 0.02). This study suggests that prophylactic PGE1 treatment may decrease the incidence of VOD in patients treated for leukaemia by allogeneic bone marrow transplantation.
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PMID:Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. 204 74

We examined the role of augmented formation of intracellular cyclic AMP (cAMP) in the mediation of stromal cell growth factor production that occurs constitutively or upon cytokine stimulation. Clonal murine marrow adherent cell lines were stimulated under serum-free conditions by interleukin-1 (IL-1) or lipopolysaccharide (LPS) and one (+/+ -1.LDA11) was found to produce low quantities of granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF identity was confirmed by the ability of supernatants from stromal cells to promote proliferation of the factor-dependent cell line FDC-P1, neutralization of this activity by antiserum to GM-CSF, and by Northern blot analysis. However, optimal concentrations of IL-1 and tumor necrosis factor-alpha (TNF-alpha), in combination, led to synergistic (greater than 5-fold higher quantity) GM-CSF production compared with either stimulus alone in the +/+ -1. LDA11 cell line, capable of GM-CSF production after only single stimulation with IL-1 or LPS. In addition, synergistic stimulation by IL-1 and TNF-alpha led to equivalent high amounts of GM-CSF in another cell line incapable of GM-CSF production after induction with only IL-1 or LPS. Any of several means to raise intracellular cAMP levels, including addition of 8-bromo-cyclic AMP (8Br cAMP) (0.25-1mM), pertussis toxin (20-100 ng/ml), or addition of prostaglandin E1 (PGE1) (1 microM), failed to stimulate GM-CSF production alone and strongly inhibited GM-CSF production in stromal cells stimulated by IL-1, LPS, or the synergistic combination of IL-1 and TNF-alpha. In addition, PGE1 and pertussis intoxication were agonists of adenylate cyclase in membranes of marrow adherent cells, whereas IL-1 and LPS were not. The role for regulators of intracellular cAMP was specific because any of the cAMP agonists alone, or in the presence of cytokine stimulators of stromal cells, strongly enhanced IL-6 production, an event known to be cAMP-responsive. Thus, acute formation of intracellular cAMP is a negative regulator of stromal cell GM-CSF production mediated by cytokines, but positively regulates IL-6 production and may be an important determinant of cytokine-directed marrow microenvironmental function. These findings on the requirement for augmentation versus inhibition of cytokine-mediated production of hemopoietic growth factors might be applied to an analysis of marrow stromal cell heterogeneity.
Leukemia 1990 Jul
PMID:Role for cyclic AMP in the postreceptor control of cytokine-stimulated stromal cell growth factor production. 216 2

Functionally active thrombomodulin (TM) was expressed in human megakaryoblastic leukemia (MEG-01s) cells. We examined the effect of agents that increased the intracellular concentration of cAMP on the expression of TM by these cells. N6,O2-dibutyryl cAMP (dbcAMP) markedly enhanced TM antigen, activity, and mRNA level in MEG-01s cells. Other agents, 8-bromo-cAMP (8BrcAMP), forskolin, and prostaglandin E1 were also effective for the enhancement. Moreover, similar enhancement of TM by these agents was also observed in another human leukemia cell line, HEL, which has megakaryocytic markers. In contrast to the marked enhancement of TM expression by these agents, the expression of the other megakaryocytic markers including platelet glycoproteins IIb/IIIa, Ib, von Willebrand factor and beta-thromboglobulin was not stimulated in MEG-01s or HEL cells. These results suggest that expression of TM is rather specifically regulated by cAMP in human megakaryocytes.
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PMID:Enhanced expression of thrombomodulin by intracellular cyclic AMP-increasing agents in two human megakaryoblastic leukemia cell lines. 216 72

Prostaglandin E1 was used to prevent veno-occlusive disease of the liver after allogeneic bone marrow transplantation for leukemia. It was given in continuous IV infusion from day -8 to day 30 after BMT at the dose of 0.3 microgram/kg/h. The patients were studied according to the risk factors of VOD: diagnosis, intensification of the conditioning and previous liver abnormalities. The diagnosis of VOD was made on at least two of the following factors: weight gain, hepatomegaly, jaundice, ascitis, pain of the right upper quadrant, increased platelet consumption. One hundred and nine patients were studied, 50 were treated by PGE1 and 59 did not receive it. Univariate analysis shows that the actuarial incidence of VOD was 12.2% in the PGE1 group and 25.5% in the non PGE1 group (P = 0.05). In acute leukemia, it was 39.1% in the non treated group and 12.8% in the PGE1 treated group (P = 0.02). Patients with previous hepatitis had an incidence of 62.5% in the non treated group and 15.5% in the treated group (P = 0.05). A positive CMV serology seemed to increase the risk of VOD: the incidence of VOD was 31.4% in non treated patients and 22% in PGE1 treated patients. The multivariate analysis of the risk factors of VOD show that unfavorable factors were: recipient positive CMV serology (P = 0.06), hepatic disease prior to transplant (P = 0.02) and the absence of PGE1 treatment (P = 0.02). This study suggests that prophylactic PGE1 treatment may decrease the incidence of VOD in patients at risk treated for leukemia by allogeneic bone marrow transplantation.
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PMID:Role of PGE1 to prevent veno-occlusive disease of the liver after bone marrow transplantation. 234 75


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