Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal and adult erythrocyte characteristics were studied serially in a 30-mo-old female with juvenile chronic myelocytic leukemia. On presentation the erythrocytes exhibited predominantly fetal characteristics as indicated by 69% hemoglobin F (HbF), 1.1% hemoglobin A2 (HbA2), absent I antigen, and fetal levels of the erythrocyte enzymes, carbonic anhydrase I and II, glucose-6-phosphate dehydrogenase, hexokinase, pyruvate kinase, and lactate dehydrogenase; 100% of the erythrocytes present contained HbF. However, Orskov-Jacobs-Stewart hemolysis demonstrated that at least one adult characteristic was present. Seven months later HbF was 17%; I antigen and carbonic anhydrase I had increased to adult levels. The number of cells containing HbF had decreased to 30%. Further studies indicated that at least three new populations of red cells were present after 7 mo which had not previously been detected. Two of these populations exhibited a mixture of both fetal and adult characteristics. Such findings suggested that an ongoing disturbance of regulatory mechanisms was responsible for the variable expression of fetal versus adult erythrocyte characteristics.
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PMID:Changing erythrocyte populations in juvenile chronic myelocytic leukemia: evidence for disordered regulation. 26 91

Haemoglobin fractions and 16 enzymatic activities of red cells of a patient with juvenile chronic myeloid leukaemia are compared to normal, to comparably reticulocyte-rich, non-neonatal and to fetal red cells. The activities of hexokinase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, monophosphoglyceromutase, enolase and glucose-6-phosphate dehydrogenase are significantly increased in fetal red cells beyond the activities of cell populations with comparable reticulocytosis. The activities of these enzymes are also increased in the patient's erythrocytes. Together with a haemoglobin F concentration of 54% and a concentration of haemoglobin Bart's of 1% these variations reflect the fetal nature of the red cells. Simultaneously, signs of dyserythropoiesis are found in the red cells of the patient: a very high activity of hexokinase and a low pyruvate kinase activity.
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PMID:Fetal erythropoiesis and dyserythropoiesis in juvenile chronic myeloid leukaemia. 82 74

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

Red cell enzymes, 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP), were evaluated in a 23-mo-old boy with juvenile chronic myelocytic leukemia (JCML) at the onset of his illness and 6 mo later during the accelerated phase. The activities of the age-dependent red cell enzymes, hexokinase, aldolase, pyruvate kinase, and glucose-6-phosphate dehydrogenase, were elevated, as were the concentrations of red cell 2,3-DPG and ATP, consistent with a young red cell population metabolizing at an increased glycolytic rate. The activities of the non-age-dependent enzymes, glyceraldehyde-3-phosphate dehydrogenase (G3PD), phosphoglycerate kinase, and enolase, were also increased to levels similar to or greater than those observed in term infants. As the illness progressed, the activity of red cell G3PD increased further, and phosphoglucose isomerase activity increased markedly. These results are consistent with the prior suggestion that JCML represents a reversion to "fetal" erythropoiesis.
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PMID:Fetal erythropoiesis in juvenile chronic myelocytic leukemia. 622 20

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