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)

Cyclic cytidine 3':5'-monophosphate (cyclic CMP), cyclic guanosine 3':5'-monophosphate (cyclic GMP), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) contents of leukocytes and urines of leukemic patients have been investigated. We have studied four types of leukemia: acute myeloblastic leukemia; chronic myelocytic leukemia; acute lymphoblastic leukemia; and chronic lymphocytic leukemia. As controls, the cyclic nucleotide content of leukocytes and urines of healthy volunteers and patients with solid tumors selected for their normal hemogram has been determined. It has also been measured in phytohemagglutinin-stimulated lymphocytes. Our data show that: (a) the concentration of cyclic CMP is always lower than that of cyclic GMP or cyclic AMP; (b) in urines, the concentrations of the three nucleotides are higher in patients than in healthy volunteers, the greatest differences being observed between the cyclic CMP concentrations of acute leukemia patients and controls; and (c) in white blood cells, cyclic AMP concentration is lower in leukemic than in normal cells. The cyclic GMP concentration is the same everywhere except in monoblastic cells and leukocytes from solid tumor patients. High cyclic CMP levels are associated only with acute leukemia, whether myeloblastic, monoblastic, or lymphoblastic, a fact which suggests that cyclic CMP could be a biochemical marker of hematopoietic stem cell malignancy.
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PMID:Relationship between the levels of cyclic cytidine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate, and cyclic adenosine 3':5'-monophosphate in urines and leukocytes and the type of human leukemias. 626 79

An endonuclease activity associated with purified proteinase K-treated intracisternal A-particles was identified and characterized. The activity required divalent cations, preferring Mn2+ to Mg2+. Salt concentrations above 50 mM inhibited the activity. The endonuclease was greatly stimulated by ATP, ADP, and dATP, whereas AMP appeared to produce a slight inhibition. GTP had no apparent effect on the activity. The enzyme introduced single-stranded nicks into DNA and nicked preferentially supercoiled DNA duplexes in the presence of ATP, although linear duplexes also functioned as substrates. Single-stranded DNA was not nicked to any great extent. The molecular weight of the enzyme was estimated to be about 40,000. The characteristics of this enzyme are very similar to those of the endonuclease found associated with Friend murine leukemia virus.
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PMID:Properties of an intracisternal A-particle-associated endonuclease activity which is stimulated by ATP. 627 25

Synergistic increases in the survival of mice bearing an L1210 leukemia tumor have been demonstrated previously after treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea together with theophylline over those treated with either agent alone. These results imply that manipulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels in L1210 cells may result in alteration of sensitivity to chemotherapy and alterations in tumor growth. In the present study, we have shown that in vivo treatment of L1210 cells with theophylline results in changes in intracellular cyclic AMP-dependent protein kinase activity levels as well as in an apparent redistribution of both the nuclear and cytoplasmic isozymes. Biochemical events in the tumor cells immediately after administration of theophylline in vivo or a cyclic AMP analog (8-parachlorophenylthio cyclic adenosine 3':5'-monophosphate in vitro were independent of the presence of 1,3-bis(2-chloroethyl)-1-nitrosourea. The changes apparently involve signal transduction via the adenylate cyclase system and manifest as: (a) increased sensitivity of cyclic AMP-dependent protein kinase to activation by cyclic AMP after treatment of L1210 cells with theophylline; (b) decrease in endogenous nuclear protein phosphorylation sites; and (c) protein kinase isozyme redistribution between nuclear and extranuclear compartments, i.e., a relative increase of the type I isozyme activity in the nuclear and of the type II isozyme activity in the 900 x g supernatant fractions after treatment of the mice with theophylline. The relative activity increases are accompanied by a relative decrease of type II activity from the nucleus and type I isozyme activity from the 900 x g extranuclear supernatant fraction. These events appear temporally related to changes in nuclear RNA metabolism as evidenced by altered kinetics of RNA precursor uptake and incorporation into tumor cell RNA after treatment. These results imply that the cyclic AMP-dependent phosphorylative modification of intracellular proteins may play a regulatory role in tumor cell growth and in theophylline-mediated tumor regression.
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PMID:Cyclic adenosine 3':5'-monophosphate-dependent protein phosphorylation and the control of leukemia L1210 cell growth. 628 49

The adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), at low concentrations (less than 10 microM), enhances the inhibitory activity of adenosine against lymphocyte-mediated cytolysis (LMC) without itself being inhibitory. At higher concentrations, EHNA alone is inhibitory to LMC with an IC50 of 160 microM. This inhibition is reversible upon washout, appears to affect an early stage of the lytic process, and does not appear to involve changes in basal levels of cyclic AMP (cAMP), ribonucleoside 5'-triphosphate pool sizes, S-adenosylhomocysteine levels, or protein carboxymethylation. EHNA does enhance the cAMP response of cytolytic lymphocytes (CL) to activators of adenylate cyclase such as prostaglandin E1. EHNA inhibits lymphocyte high-affinity cAMP phosphodiesterase at immunosuppressive levels, exhibiting hyperbolic mixed-type inhibition (Ki = 83 microM, alpha = 0.47, beta = 0.18). Whereas inhibition of intralymphocytic ADA is complete at low concentrations (less than 25 microM) of EHNA, inhibition of LMC and intralymphocytic cAMP phosphodiesterase increases linearly with EHNA concentration to at least 200 microM. The presence of 200 microM EHNA during the centrifugation of mixtures of CL and EL4 leukemia target cells leads to increased CL cAMP levels. 2'-Deoxycoformycin, a more potent ADA inhibitor than EHNA, is not inhibitory to LMC and shows none of these cAMP-related effects. These results suggest that CL-target cell contact stimulates adenylate cyclase in the CL and that EHNA inhibits LMC due to its enhancement of this target cell-stimulated elevation of cAMP.
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PMID:Inhibition of lymphocyte-mediated cytolysis and cyclic AMP phosphodiesterase by erythro-9-(2-hydroxy-3-nonyl)adenine. 629 34

The effect of Escherichia coli heat-stable (ST) enterotoxin on calcium and cyclic nucleotide metabolism in rat basophilic leukemia cell cultures was investigated. Addition of ST enterotoxin to rat basophilic leukemia cell cultures resulted in dose- and time-dependent stimulation of calcium uptake and elevation of the intracellular cyclic GMP (cGMP) concentration. The effect of ST enterotoxin on calcium uptake (P less than 0.02) and cGMP synthesis (P less than 0.02) was demonstrated after 5 and 30 min of incubation at 37 degrees C, respectively. In further studies ST enterotoxin did not enhance calcium release or the intracellular concentration of cyclic AMP. The stimulation of calcium uptake and cGMP synthesis by ST enterotoxin was inhibited by pharmacological and chemical agents which block cellular calcium entry and prostaglandin synthesis. These results demonstrate that ST enterotoxin induces calcium uptake and cGMP synthesis in rat basophilic leukemia cell cultures.
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PMID:Stimulation of calcium uptake and cyclic GMP synthesis in rat basophilic leukemia cells by Escherichia coli heat-stable enterotoxin. 630 75

Plasma levels of cyclic AMP and cyclic GMP were determined in 35 guinea pigs for up to 9 days following subcutaneous passage of L2C leukemia cells. Twenty guinea pigs into which normal syngeneic guinea pig thymocytes were passaged served as controls. Cyclic AMP levels in plasma showed little change and were only elevated significantly in test animals on day 9 after passage. In contrast cyclic GMP levels reached a maximum on day 5 after passage of leukemia cells with two to threefold rises over day 1 levels. Increases in leukocyte counts were not observed until day 7 in test animals. Of the other tumour growth indices which were examined, the axillary (draining) node index gave the earliest indication of cell proliferation, with significant elevations on day 3 after passage. The authors conclude that plasma cyclic GMP increases precede increases in white cell counts by at least 2 days, and may reflect an early increase in axillary node growth.
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PMID:Changes in guinea pig plasma cyclic nucleotide levels during the development of a transplantable leukemia. 631 60

Cholera enterotoxin (CT), at an optimal concentration of 2.38 X 10(-10) M, stimulated calcium uptake (P less than 0.01) and cyclic AMP accumulation (P less than 0.02) in cultured rat basophilic leukemia cells. No significant effect of CT on calcium release or cyclic GMP accumulation was detected. Pharmacologic and chemical agents which block calcium uptake or prostaglandin synthesis antagonized the effect of CT.
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PMID:Effect of cholera enterotoxin on calcium uptake and cyclic AMP accumulation in rat basophilic leukemia cells. 632 Dec 61

A distribution picture was prepared on the basis of the correlation between peroxidase activity and cell size in leukemic cells using an automated leukocyte differential counter (Hemalog-D). From this, acute nonlymphocytic leukemia was classified into three groups in which the therapeutic response was examined. The leukemic cells of Group I were medium or large and were negative or weakly positive to peroxidase. These cells were characterized by their location in the upper part of the normal lymphocyte distribution. The leukocyte differential count, measured by a computer on the basis of the distribution picture, showed an increase in large unstained cells (LUC) and lymphocytes. The leukemic cells of Group II were large and positive to peroxidase and were characterized by their location in the right upper part, across the region of LUC, monocytes, basophil and neutrophil leukocytes as seen in the distribution picture. The findings of Hemalog-D showed an increase in LUC, remainder and neutrophil leukocytes. The leukemic cells of Group III were medium-sized and moderately or strongly positive to peroxidase. This group was characterized by their location in the lower part of normal neutrophil leukocytes and Hemalog-D showed an increase in neutrophil leukocytes. A total of 71 patients with acute nonlymphocytic leukemia were assessed according to this classification. Group I (14 patients): 11 with acute myelogenous leukemia (AML), 2 with acute monocytic leukemia (AMoL) and 1 with acute myelomonocytic leukemia ( AMMoL ); Group II (17 patients): 7 with AML and 10 with AMoL; Group III (40 patients): 28 with AML, 4 with AMoL, 1 with AMMoL and 7 with acute promyelocytic leukemia (APL). These groups were treated with the protocol (DCMP two step, BH-AC DMP, BH-AC AMP) established by the Yamada Leukemia Study Group of the Japan Welfare Ministry Cancer Research Project (chairman Yamada, K). The complete remission rate was 35.7% in Group I, 58.8% in Group II and 85.0% in Group III. The difference between Groups I and III was statistically significant (P less than 0.005), as was the difference between Groups II and III (P less than 0.1), while that between Groups I and II was not significant. The median survival was 12 months in Group I, 9 months in Group II and 15 months in the Group III and the difference between Groups I and III was statistically significant (P less than 0.05). Group III included a small number of AMoL and APL patients in addition to AML, while Groups I and II consisted mainly of patients with AMoL and AML.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Classification of acute non-lymphocytic leukemia according to the distribution picture of peroxidase activity and cell size: correlation between the classification and therapeutic response. 658 10

The human leukemia cell line HL60 which resembles promyelocytes can be induced to differentiate to cells displaying features of the mature myeloid phenotype by a variety of agents including retinoic acid (RA) and agents that elevate intracellular adenosine 3:5 cyclic monophosphate (cyclic AMP) levels, e.g., 8-bromo-cyclic adenosine 3:5 monophosphate (8-Br-cyclic AMP), cholera toxin. Since most, if not all the effects of cyclic AMP, are mediated by adenosine 3:5 cyclic monophosphate-dependent protein kinase (cyclic AMP-dPK), we investigated the role of cyclic AMP-dPK and adenosine 3:5 cyclic monophosphate-independent protein kinase (cyclic AMP-iPK) in the induced differentiation of HL60 cells. Marked stimulation of cyclic AMP-dPK and cyclic AMP-iPK appears to be intimately involved with and specific for HL60 myeloid differentiation as evidenced by: (1) Stimulation of cyclic AMP-dPK and cyclic AMP-iPK early during HL60 myeloid differentiation and prior to phenotypic changes. (2) RA and dimethylformamide (DMF), agents that induce differentiation along the myeloid pathway, cause a marked increase in the type l cytosolic cyclic AMP-dPK and cyclic AMP-iPK (protamine kinase) while no such increases are noted in cells treated with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) which induces differentiation along the monocyte/macrophage pathway. (3) Both native polyacrylamide gel electrophoresis as well as photoaffinity labeling with 8-azido-cyclic AMP demonstrate marked increases in type l cyclic AMP-dPK in the cytosols of cells exposed to agents that induce myeloid differentiation but no increase in TPA-differentiated cells. (4) The appearance and disappearance of specific cyclic AMP-dependent and -independent protein phosphorylations are associated with the induced myeloid differentiated state.
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PMID:Cyclic AMP-dependent and -independent protein kinases and protein phosphorylation in human promyelocytic leukemia (HL60) cells induced to differentiate by retinoic acid. 658 51

Sixteen of 20 patients(80%) with adult ANLL treated with B H-AC X AMP therapy attained complete remission (CR). According to the FAB classification, CR rate was 6 out of 8 (75%) for M1, 3 out of 5 (60%) for M2, 2 out of 2 (100%) for M3, and 5 out of 5 (100%) for M4. The median of remission duration in 16 patients who attained CR was 8 months and appeared to be longer in patients with M2, rather than other types, of leukemia than in those with the other types of leukemia. BH-AC X AMP therapy is highly effective for remission induction in adult ANLL and long term disease free survival could be expected by addition of appropriate maintenance therapy.
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PMID:[Combination chemotherapy of N(4)-behenoyl-1-beta-arabinofuranosylcytosine, aclarubicin, 6-MP, and prednisolone (BH-AC. AMP therapy) for adult acute non-lymphocytic leukemia]. 658 25


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