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)

A congenital erythrocyte pyruvate kinase (PK) deficiency was found in a 72-year old female patient with chronic myelomonocytic leukemia (CMML). Erythrocyte PK deficiency was associated with an increase in the activity of hexokinase, 6-phosphogluconate dehydrogenase and glutathione peroxidase in erythrocytes as well as a decrease in acetylcholinesterase, glutathione reductase and glucosephosphate isomerase activities. The enzymatic abnormalities were accompanied by alterations in hemoglobin and in i antigen content of erythrocyte membrane. In addition, bone marrow ultrastructural studies showed dyshemopoietic changes in all blood cell lines and especially in erythroblasts. The present findings confirm the close relationship between CMML and acquired dyserythropoietic syndromes and constitute a new observation of the infrequent association of hereditary erythrocyte enzymopathies and leukemia. A survey of the literature is presented.
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PMID:Chronic myelomonocytic leukemia associated with hereditary pyruvate kinase deficiency and multiple acquired erythrocyte abnormalities. 10 94

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6 phosphate glucono dehydrogenase (6 phospho-D-gluconate: NADP oxidoreductase, 6PGD) lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH), glutamate oxaloacetate transaminase (L-aspartate: 2-oxo-glutarate aminotransferase, GOT) and hexokinase (ATP: D-hexo-6-phosphotrans-ferase, Hx) were measured over 24 h in isolated lymphocytes of normal subjects and in white cells of patients with chronic lymphatic leukaemia (CLL). The activitty patterns of all enzymes in the normal lymphocytes were similar. A computed pattern of all the results exhibited a circadian rhythm of activity with the highest level at 16.00 hours. The oscillations in the activities of the same enzymes in the CLL cells differed among the patients, although all the enzymes of the same individual showed a similar diurnal rhythmic pattern. All peaks in this group appeared between 20.00 and 08.00 hours. The possible importance of these observations in setting up therapeutic schedules was raised.
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PMID:Blood leucocyte enzymes. III. Diurnal rhythm of activity in isolated lymphocytes of normal subjects and chronic lymphatic leukaemia patients. 98 50

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D-hexose 6-phosphotransferase, Hx), lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH). glutamate oxaloacetate transaminase (L-aspartate: 2 oxoglutarate aminotransferase, GOT) and dihydrofolate reductase (DHFR) were measured at 8 a.m. in leucocytes of healthy individuals and patients with chronic myeloid leukaemia (CML), chronic lymphatic leukaemia (CLL), myelofibrosis with myeloid metaplasia and polycythaemia vera. In view of the heterogeneity of the leucocyte populations in these conditions, the enzyme activities were correlated to the number of immature cells in CML and to the percentage of lymphocytes in CLL. No differences in the enzyme activities were found between the white cells of healthy individuals, myelofibrosis with myeloid metaplasia and polycythaemia vera. In CML the activities of all enzymes except GOT correlated directly with the number of immature cells; an inverse correlation with the number of lymphocytes was observed in CLL. GOT was the only enzyme whose activity correlated with the number of lymphocytes in the cell suspension. Furthermore, a significantly higher activity of this enzyme was found in Ficoll-isolated CLL lymphocytes as compared to normal lymphocytes.
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PMID:Blood leucocyte enzymes. II. Activities at 8-9 a.m. in cells of normal subjects, chronic lymphatic leukaemia and chronic myeloid leukaemia patients. 105 70

Many hormonal, neurotransmitter, and sensory stimuli trigger the formation of inositol 1,4,5-trisphosphate, which in turn releases calcium from intracellular stores. We report here that inositol 1,4,5-trisphosphate-induced calcium release from saponin-permeabilized rat basophilic leukemia cells at 37 degrees C is markedly biphasic, in contrast with nearly monophasic release kinetics at 11 degrees C. Hepatoma, PC-12 neuronal cells, and several other cell types exhibit similar biphasic release at 37 degrees C. The biphasic kinetics are not due to degradation of inositol 1,4,5-trisphosphate or to increased Ca2(+)-ATPase pump activity. Biphasic calcium release was also seen when ATP was quenched to less than 0.4 microM by adding hexokinase and glucose, suggesting that phosphorylation is not involved. External calcium (100 nM-600 nM) range had little influence on the biphasic kinetics. Rapid-mixing experiments revealed that rapid efflux of calcium is followed in approximately 0.5 s by a 30-fold slower efflux. Most striking, successive additions of the same amount of inositol 1,4,5-trisphosphate induced short bursts of calcium release of similar size. This retention of responsiveness, which we term increment detection, may be a distinct mode of signal transduction. Like inactivation and adaptation, increment detection gives rise to transient responses to sustained stimuli. Systems exhibiting inactivation, adaptation, and increment detection differ in their responsiveness (none, partial, and full, respectively) to stepwise increases in stimulus intensity. Increment detection could be advantageous in generating receptor-triggered calcium oscillations.
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PMID:Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate. 233 24

Exponentially growing human lymphoblasts (culture LS-2) were separated by cell sorting (FACS II, Becton Dickinson) according to their deoxyribonucleic acid (DNA) content, designating them at particular phases of the cell cycle. Prior to cell sorting the DNA has been fluorochrome-labeled with the Hoechst stain H 33342. Maximum cell enrichments of 94% for G0 + G1 cells, 96% for S cells and 74% for G2 + M cells could be achieved. The enzyme activities of thymidine kinase (TK), thymidylate synthase (TS), DNA polymerase (DNA-P), dihydrofolate reductase (FH2-R), methionine synthase (MS), and hexokinase (HK) were determined in the obtained cell fractions. Although incorporation of 3H-thymidine (3H-dTR) and the 3H-dTR labeling index were significantly inhibited by the dye, no evidence of cell staining's having a significant effect on the enzyme activities was found. The enzyme activities for approximately 100% pure G0 + G1, S, and G2 + M cells were computed. With exception of TK, all the enzymes under study were shown to exhibit activities--although of differing degree--in the G0 + G1, S, and G2 + M cells. No TK activity was shown in G0 and G1 cells; its activity, however, was approximately the same in S and G2 + M cells. This applies likewise for TS which, in contrast to TK, exhibits minor activity in G0 + G1 cells. DNA-P was highly active in G0 + G1 cells, but maximum activity was in S cells. FH2-R exhibited maximum activity in S cells, although the difference in activity between S and G2 + M cells was not significant. None of the observed differences in MS activity was significant, indicating equally high activity in cells of all cell cycle phases. HK activity is approximately twice as high in G2 + M cells as in G0 + G1 cells.
Leukemia 1989 May
PMID:Relation between cell cycle stage and the activity of DNA-synthesizing enzymes in cultured human lymphoblasts: investigations on cells separated according to DNA content by way of a cell sorter. 271 50

Mannose in animal cells is phosphorylated by hexokinase (HK) and later isomerised by mannose phosphate isomerase (MPI) to fructose-6-P, which is incorporated in the glycolysis pathway. In this paper we report a significant decrease of MPI activity in splenic lymphoid cells from AKR/J old mice with lymphocytic leukaemia in comparison to that found in splenic lymphocytes from AKR/J non-leukaemic young mice and BALB/c young and old control mice. However, HK with mannose as substrate presents a normal activity in AKR/J leukaemic mice. This marked shortage of MPI explains the in vitro mannose toxicity found by us here in splenic lymphoid cells from AKR/J leukaemic mice. MPI activity was also decreased in peripheral blood lymphocytes from 4 out of the 6 patients studied with chronic lymphocytic leukaemia in relation to the activity found in the lymphocytes from healthy donors. The utility of analysing MPI activity in leukaemia patients and the use of mannose as an innocuous chemotherapic supporting agent in patients with decreased MPI activity is proposed.
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PMID:Enzymes of mannose metabolism in murine and human lymphocytic leukaemia. 321 65

Undifferentiated human lymphoblasts (culture LS-2) were separated according to cell size during their exponential growth phase by way of centrifugal elutriation. The cell fractions thus obtained were characterized in terms of different cell cycle stages by flow cytometric measurement of their deoxyribonucleic acid (DNA histogram), the [3H]thymidine labeling index, and by determining the rate of [3H]thymidine incorporation. In these cell fractions the activities of thymidine kinase, thymidylate synthase, DNA polymerase, dihydrofolate reductase, methionine synthase, and hexokinase were determined. The results showed that all the enzymes investigated exhibited activities in all cell fractions. With the exception of DNA polymerase, all of the enzymes exhibited the lowest level of activity in the fraction containing the highest proportion of G0 + G1 phase cells (fraction 2); the activity of thymidine kinase was particularly low. This would suggest that thymidine kinase is not active in G0 + G1 phase cells and that the activity measured in fraction 2 is perhaps attributable to contamination of this fraction by S and G2 + M phase cells.
Leukemia 1987 Mar
PMID:Relation between cell cycle stage and the activity of DNA-synthesizing enzymes in cultured human lymphoblasts: investigations on cell fractions enriched according to cell cycle stages by way of centrifugal elutriation. 366 41

Adriamycin is used for the treatment of leukemia and other neoplastic processes. Unfortunately the drug has a toxic effect on some tissues. Cardiotoxicity in particular limits the use of the drug. Several hypotheses have been given to explain adriamycin heart toxicity. The authors have studied the effect of the drug on the enzymes isocitrate dehydrogenase-NADP, malic enzyme, 6-P-gluconate dehydrogenase, malic dehydrogenase-NAD+, hexokinase, and phosphofructokinase. They observed that adriamycin inhibits the NADP-dependent enzymes, and that the sulfhydryl group of the enzymes may be involved in the inhibitory action of adriamycin.
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PMID:[Study of the inhibition produced by adriamycin against specific enzymes in the rat heart]. 610 Apr 65

The expression of fetal characteristics of erythropoiesis (haemoglobin F concentration, haemoglobin A2 concentration, haemoglobin F cells, globin chain synthesis, carboanhydrase isoenzyme B, hexokinase isoenzymes, erythrocyte membrane antigens of the iI- and the ABH-system) was examined in red cells of twelve patients with different bone marrow disorders (juvenile chronic myeloid leukaemia (JCML), erythroleukaemia (EL), acute myelogenous leukaemia (AML), aplastic anaemia (AA) and Diamond-Blackfan anaemia (DB)). In JCML and EL all red cell parameters studied appeared to be fetal including the distribution of hexokinase isoenzymes. No fetal signs could be found in red cells of patients with AML. In two patients with DB who were treated by transfusion no fetal erythropoiesis could be detected. In one patient with DB under cortisone treatment i-antigen, ABH-antigens, haemoglobin F concentration, globin chain synthesis and hexokinase isoenzyme distribution were of the fetal or mixed type. In patients with AA only slight elevations of haemoglobin F were detectable. The nearly total reversion to fetal erythropoiesis in JCML and EL seems to be a part of the disorder itself, whereas in the other disorders the reactivation of fetal erythropoiesis could be the result of an erythropoietic stress.
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PMID:The pattern of reactivated fetal erythropoiesis in bone marrow disorders of childhood. 696 27

Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.
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PMID:Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. 1148 2


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