Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease.
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PMID:Elevated serum manganese superoxide dismutase in acute leukemias. 159 65

An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD.
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PMID:Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody. 231 2

The activity, content and true specific activity of superoxide dismutase (SOD) were determined for human erythrocytes of 105 normal healthy subjects. At the same time the activities of erythrocyte SOD are also determined in patients with lung cancer, lymphoma, leukemia and thyroidal dysfunctions. The mean SOD activity of healthy subjects assayed by the method of inhibition of xanthine autoxidation was 11.0 X 10(3) units/g of hemoglobin (Hb). The mean SOD content of healthy subjects assayed by an immunodiffusion method was 456 micrograms/g of Hb. Both the activity and the content of SOD showed normal distributions, while no significant variations in regard to sex and age were detected. A high positive correlation between the activity and the content of SOD was observed in normal healthy subjects (r = 0.77, p less than 0.001). True specific activity was calculated from the levels of activity and content of SOD. The mean true specific activity of SOD in human erythrocytes was 23.7 units/micrograms of SOD. There was no significant difference in true specific activity among age groups. The activity of erythrocyte SOD was determined in 38 patients with lung cancer (n = 15), malignant lymphoma (n = 11) and acute myeloid leukemia (n = 12). Patients with malignant lymphoma and acute myeloid leukemia showed a significant decrease in enzyme activity (p less than 0.01) while the patients with lung cancer (9 squamous cell carcinomas and 6 small cell carcinomas) showed a normal value of SOD activity. Furthermore, patients with malignant lymphoma and acute myeloid leukemia who were in remission and were not being treated with anticancer drugs also showed a significant decrease in SOD activity. These observations therefore indicate that a low level of erythrocyte SOD activity is related to cancer and that degree of the activities varies with the type of cancer. A total of 18 determinations of erythrocyte SOD activity were made on 16 patients with thyroidal dysfunction. Patients with hyperthyroidism showed a significant increase in SOD activity (p less than 0.01), while patients with hypothyroidism showed the same SOD activity as those of healthy subjects. A significantly high positive correlation was found between erythrocyte SOD activity and the level of thyroxine in serum (r = 0.60, p less than 0.01). The author suggests therefore that erythrocyte SOD activity has a close relationship to the state of the thyroid hormones.
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PMID:Superoxide dismutase level in human erythrocytes and its clinical application to the patients with cancers and thyroidal dysfunctions. 361 27

The activity of erythrocyte superoxide dismutase (SOD) and catalase was determined in 38 patients with lung cancers (n = 15), malignant lymphoma (n = 11) and acute myeloid leukemia (n = 12). The patients with malignant lymphoma and acute myeloid leukemia showed a significant decrease in both enzyme activities (P less than 0.01) while the patients with lung cancer (9 squamous cell carcinomas and 6 small cell carcinomas) showed normal values of SOD and catalase activities. Furthermore, the patients with malignant lymphoma and acute myeloid leukemia, in remission, but not treated with anticancer drugs, also showed a significant decrease in SOD and catalase activity. These observations therefore indicate that a deficiency of erythrocyte SOD and catalase activities is caused by cancer and varies with the type of the cancer.
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PMID:Deficiency of erythrocyte superoxide dismutase and catalase activities in patients with malignant lymphoma and acute myeloid leukemia. 609 9

Superoxide dismutase activity was determined in leukemic blasts of 24 patients with acute leukemia and was correlated to its type. The activity was significantly lower in five patients with T cell or B cell leukemia, and there was a wide range of distribution in 15 patients with non-T, non-B cell leukemia. Manganese superoxide dismutase activity was significantly lower in all types of acute lymphoblastic leukemia than in normal mononuclear leukocytes. Both total and manganese superoxide dismutase activities in acute myeloblastic leukemia, however, were significantly higher than those in normal polymorphonuclear leukocytes. The prognosis in patients with a low superoxide dismutase activity in leukemic blasts seemed to be poorer. Determination of superoxide dismutase activity in leukemic blasts may have a prognostic value in the management of children with acute leukemia.
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PMID:Superoxide dismutase activity in leukemic blasts of children with acute leukemia. 660 5

We have previously reported that intracellular tumor necrosis factor (enTNF) is responsible for resistance, in established cell lines to doxorubicin (DOX), exogenous TNF, and heat stress by inducing manganous superoxide dismutase (MnSOD), thereby scavenging reactive oxygen free radicals. Leukemic cells from 19 patients (6 acute lymphoblastic leukemia, 13 acute myeloid leukemia) were examined for their sensitivity to DOX and TNF in relation to their enTNF expression and MnSOD activity. Sensitivity to DOX and the expression of enTNF or MnSOD activity were inversely correlated. In a case with acquired resistance to chemotherapy which included DOX, enTNF expression and MnSOD activity were increased. Furthermore, in 14 cases treated with a regimen including an anthracycline, 4 cases that failed to respond to chemotherapy showed relatively high amounts of enTNF expression. KG-1 (human acute myelogenous leukemia) cells transfected with a nonsecretory-type TNF expression vector (pTNF delta pro) showed resistance to DOX. A significant increase in MnSOD levels was also noted in the transfectants. TNF antisense cDNA was transfected into isolated leukemic cells from five patients. Sensitivity of the antisense transfectants to DOX was increased, approximately 1.4- to 2.5-fold. These results suggest that enTNF acts as a resistance factor against DOX in leukemia, and that enTNF may be useful as a predictor of DOX sensitivity in leukemia.
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PMID:Endogenous tumor necrosis factor as a predictor of doxorubicin sensitivity in leukemic patients. 911 91

Sensitivity to doxorubicin (DOX) and expression of intracellular endogenous TNF (enTNF) or manganous superoxide dismutase (MnSOD) activity were found to be inversely correlated in leukemic cells from 19 patients (6 acute lymphoblastic leukemia, 13 acute myeloblastic leukemia). In a case with acquired resistance to chemotherapy which included DOX, enTNF expression and MnSOD activity were increased. Furthermore, in 14 cases treated with a regimen including an anthracycline, 4 cases which failed to respond to chemotherapy showed relatively high amounts of enTNF expression. After TNF antisense cDNA was transfected into leukemic cells isolated from 5 patients, sensitivity of transfectants to DOX increased 1.4- to 2.5-fold. Overall, we found enTNF to act as a resistance factor against DOX in leukemia which may predict response to DOX.
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PMID:Endogenous tumor necrosis factor and doxorubicin sensitivity in leukemic patients. 971 10

The high event-free survival rates of Down syndrome (DS) children with acute myeloid leukemia (AML) are due, in part, to increased in vitro sensitivity of DS myeloblasts to cytosine arabinoside (ara-C) and daunorubicin and the greater generation of ara-C triphosphate (ara-CTP) from ara-C compared with myeloblasts from non-DS patients (Taub et al, Blood 87:3395, 1996). This study further explores the molecular basis of chemotherapy sensitivity of DS AML patients by examining the expression of chromosome 21-localized genes in myeloblasts from newly diagnosed AML patients. Transcript levels of two chromosome 21-localized genes, cystathionine-beta-synthase (CBS) and superoxide dismutase (SOD), measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), were 12.0- and 3. 8-fold higher in DS compared with non-DS myeloblasts (P <.0001 and P <.0001, respectively). Conversely, there were no significant increases in transcripts for 2 other chromosome 21-localized genes, carbonyl reductase and the reduced folate carrier. CBS transcript levels correlated with both in vitro ara-C sensitivity measured by the 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium-bro mid e (MTT) assay (P =.003) and the generation of (3)H-ara-C triphosphate (ara-CTP) after in vitro incubations with 5 micromol/L (3)H-ara-C (P =.0003). Transcripts of deoxycytidine kinase were 2.6-fold higher in DS compared with non-DS cells and may be a factor in the enhanced metabolism of ara-C in DS cells. There was no significant correlation of SOD transcripts with in vitro ara-C and daunorubicin sensitivities. Increased CBS transcripts could result in elevated CBS activity, which modulates ara-C metabolism by altering reduced folate pools, deoxycytidine triphosphate pools, S-adenosylmethionine levels, and/or methylation of the deoxycytidine kinase gene. The further identification of the molecular mechanisms of chemotherapy sensitivity of DS AML patients may lead to significant improvements in the treatment and cure of AML.
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PMID:Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. 1043 27

Reactive oxygen species (ROS)-specific mechanisms of drug resistance were explored in paraquat (PQ)-resistant acute myelogenous leukemia cell (OCI/AML-2) sublines. For this, PQ-resistant AML sublines, AML-2/PQ100 and AML-2/PQ400, were selected in the presence of PQ concentrations of 100 microg/ml and 400 microg/ml, respectively. They showed a moderate level of cross resistance to cisplatin and doxorubicin. They were also slightly more resistant than the parental cell (AML-2/WT) to etoposide, camptothecin and daunorubicin. The resistance of PQ-resistant AML-2 sublines to cisplatin seemed to be due to increased amounts of metallothionein, which was not only supported by reversal of resistance to cisplatin by propargylglycin (an inhibitor of metallothionein synthesis) but also confirmed by Western blot analysis and reverse transcription-PCR assay. In addition, both AML-PQ100 and /PQ400 sublines showed increased activities of Cu-, Zn-containing superoxide dismutase (Cu,Zn-SOD) and Mn-containing superoxide dismutase (Mn-SOD), whereas AML-2/PQ400, but not AML-2/PQ100, showed increased glutathione S-transferase activity as compared to that of AML-2/WT. However, there was no difference in other ROS-related cellular antioxidants between AML-2/WT and its PQ-resistant sublines. Taken together, these results strongly suggest that increases in levels of metallothionein, glutathione S-transferase, Cu,Zn-SOD and Mn-SOD play important roles in protective mechanisms against toxicity of PQ or ROS in AML cells.
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PMID:Reactive oxygen species-specific mechanisms of drug resistance in paraquat-resistant acute myelogenous leukemia sublines. 1077 45

The purpose of this study was to investigate the adaptive mechanisms of hydrogen peroxide-supersensitive AML cells against the reactive oxygen species (ROS). Their scavenging capacity against ROS was determined using a fluorometric probe in the doxorubicin-resistant AML-2/DX100 cell characterized by the down-regulation of catalase. AML-2/DX100 cells had more scavenging capacity against endogenous pro-oxidants than did the parental cells AML-2/WT, suggesting that an anti-oxidant adaptation against ROS occurred. cDNA microarrays for 8000 human genes revealed that among 21 anti-oxidant genes, each four gene was up- and down-regulated more than 1.5-fold in AML-2/DX100 compared with AML-2/WT. The mRNA expression of glutathione S-transferase Pi, peroxiredoxin 2, thioredoxin 2, and glutaredoxin was elevated whereas that of peroxiredoxin 3, metallothionein-1F, superoxide dismutase 2, and thioredoxin reductase 1 was depressed. The result indicates that the down-regulation of certain anti-oxidant mechanisms can be compensated for by the up- and down-regulation of the other anti-oxidant mechanisms.
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PMID:Anti-oxidant adaptation in the AML cells supersensitive to hydrogen peroxide. 1515 39


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