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)

Neutrophils and band forms from patients with acute myeloid leukemia and myelodysplastic syndrome were stained for the presence of myeloperoxidase using a cytochemical method (diaminobenzidine/hydrogen peroxide) and the alkaline phosphatase--anti-alkaline phosphatase immunocytochemical procedure (using monoclonal anti-myeloperoxidase). Neutrophils and bands were also stained for elastase and lactoferrin using monoclonal and polyclonal antibodies, respectively. Subpopulations of neutrophils and bands from cases of acute myeloid leukemia and myelodysplasia exhibited a qualitative and/or quantitative deficiency in myeloperoxidase. In addition, a quantitative decrease in elastase and/or lactoferrin staining was detected. Thus, neutrophils and bands from patients with acute myeloid leukemia and myelodysplastic syndrome have a defect in one or more of the constituents of primary and/or secondary granules. These defects are consistent with the view that abnormal neutrophils and bands are derived from a malignant clone of myeloid precursor cells.
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PMID:Abnormal neutrophils in acute myeloid leukemia and myelodysplastic syndrome. 283 2

A continuous tissue culture cell line (Karpas line 120), derived from a patient with acute myeloblastic leukemia, not only demonstrates myeloblastic morphology and in vitro expression of several myeloid-specific biochemical markers but also contains Epstein-Barr virus (EBV) nuclear antigen. The present studies demonstrate EBV-genome-specific DNA within the total cellular DNA by molecular hybridization, thus establishing the presence of stable viral genome integration. The cells demonstrate complex coordinated myeloid functions including ingestion, degranulation, and respiratory burst activity. Line 120 cells show a respiratory burst (superoxide and hydrogen peroxide generation and hexosemonophosphate shunt activity) in response to soluble (phorbol myristate acetate) and particulate (latex beads) stimuli, as do normal granulocytes. They ingest complement-opsonized particles (lipopolysaccharide-oil droplets, zymosan, and bacteria), and degranulate in response to them. However, unlike normal granulocytes, the line 120 cells do not demonstrate respiratory burst activity in response to these complementopsonized particles. The dissociation between ingestion of complement-opsonized particles and activation of oxygen-dependent bactericidal activity severely impairs bacterial killing as compared with normal polymorphonuclear phagocytes.
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PMID:Dissociation of opsonized particle phagocytosis and respiratory burst activity in an Epstein-Barr virus-infected myeloid cell line. 624 64

The first 10 bone marrow transplantations (BMT), 6 of the allogenic (allo-BMT) and 4 autologous (auto-BMT) were performed from February to June 1994 in Byelarus Center for Bone Marrow Transplantation. Two of the patients were experiencing the first complete remission of acute lymphoblastic leukemia (ALL), one of them - the first ALL recurrence, three patients with acute myeloblastic leukemia had the first complete remission, four patients had a chronic phase of chronic myeloid leukemia. In auto-BMT bone marrow (BM) was stored in liquid hydrogen after programmed freezer. An average yield of nucleated cells (NC) after taking and separation of allo-BM made up 3.0 x 10(8) cell/kg and 2.7 x 10(8) cell/kg in auto-BMT. After thawing of BM NC yield reached 1.5 x 10(8) cell/kg (0.8-2.3) x 10(8) cell/kg. CFU concentrations persisted at 24.7 x 10(4) (5.0-40.4) x 10(4) cell/kg body weight. The mean duration of leukocyte, neutrophil and platelet rise to the levels of over 1.0 x 10(9)/l, 0.5 x 10(9)/l, 20 x 10(9) cell/l, respectively, and the last time red cells were transfused were 23 (19-33), 23 (19-31), 22 (9-51), 4.5 (0-19), respectively. One ALL (first complete remission) patient died on day 52 after allo BMT of severe hepatic venous-occlusive disease. The other ALL patient (the first relapse) developed another relapse on day 112 after BMT. The rest 8 patients are in satisfactory condition.
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PMID:[First results of bone marrow transplantation in acute and chronic leukemia at the Byelarus Center for Bone Marrow Transplantation]. 759 68

D-penicillamine (PSH) is a copper chelator that generates hydrogen peroxide and inhibits neovascularization. As hydrogen peroxide is toxic to some tumor cells and to blood vessels, we reasoned that PSH plus copper would inhibit tumors in vivo and in vitro. To test this hypothesis, we first incubated murine J558L plasmacytoma cells with varying combinations of drug (PSH and/or copper sulfate) plus modulators (fetal calf serum, dithiothrietol, catalase, eosinophil peroxidase) and then used fluorescence microscopy to measure cell proliferation, necrosis, and apoptosis. We also incubated various types of human tumor cells with PSH plus copper for 24 hours and then measured the number of surviving cells 24 hours later. For the in vivo studies, we measured the effects of 7 daily i.p. injections of 10 mg of PSH on the growth rates of interleukin-5 genetransfected J558L tumors in 20 BALB/c mice. Our experiments demonstrated that PSH plus copper exerted a significant antiproliferative effect on tumor cells in vitro that was neutralized by protein or catalase and enhanced by adherent eosinophil peroxidase. Human acute myelogenous leukemia cells were especially sensitive to PSH plus copper. In vivo, however, PSH had no significant effect on the growth rates of J558L tumors that were infiltrated by eosinophils. We conclude that the interaction of PSH-copper with tumors is primarily antiproliferative, mediated by hydrogen peroxide, and inhibitable by protein. Therefore, for PSH to be an effective antineoplastic drug strategies will need to be developed to prevent its rapid neutralization by protein.
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PMID:In vitro and in vivo interactions of D-penicillamine with tumors. 870 40

Cell death by apoptosis is often accompanied by extensive DNA cleavage at internucleosomal linker sites. Thus, the foremost techniques for estimating apoptosis are based on biochemical, electrophoretic, or flow cytometry analysis of nuclear DNA. However, apoptosis is also associated with a chain of morphologic changes in the nuclear and cytoplasmic structures that are easily recognizable using light microscopy. We suggest that changes in morphology of cells undergoing apoptosis might cause characteristic changes in their optical properties. It follows that continuous measuring of the OD of cells undergoing apoptosis would enable the study of the kinetics of cell death. We recently described an automated microculture kinetic (MiCK) assay that provides multiple OD measurements in nondisrupted cell cultures. In the present study the MiCK assay was employed to follow OD changes in HL-60 and OCI/AML-3 myelogenous leukemia cells and murine thymocytes exposed to ethanol, hydrogen peroxide, etoposide, cisplatin, doxorubicin, or hyperthermia; i.e., divers stimuli known to induce cell death via apoptosis or necrosis. The MiCK assay revealed prominent differences between the optical properties of the cells undergoing the two different modes of death. Plotting the OD data accumulated during the assay period against time betrayed characteristic patterns of either "apoptotic" or "necrotic" OD curves. The best fit slope of the indicative of apoptosis steep rising component of the apoptotic curve, correlated directly with the percentage of morphologically apoptotic cells in the culture. Criteria for graphical estimate of apoptosis were suggested and used to study apoptosis induced in HL-60 cells by the chemotherapy compounds etoposide and cisplatin. The MiCK assay demonstrated markedly varying time courses of the cell apoptotic response to these two drugs. In both cases, however, the time of graphically predicted peaks of apoptosis correlated with the time of morphologically and electrophoretically recognized peaks of apoptosis. Adaptability of the MiCK assay to a 96-well microplate format opens the way for large-scale studying of cell apoptotic response to various stimuli. An important technical advantage of the automated MiCK assay of apoptosis is that it does not require additional laboratory procedures after microcultures are initiated.
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PMID:Automated monitoring of apoptosis in suspension cell cultures. 878 Jan 73

Mucormycosis is a devastating fungal disease affecting mainly diabetic and immunosuppressed patients and frequently causing death. Mucor rhizopus, the opportunistic fungus, has been controlled via radical extirpation and intravenous Amphotericin B. Hyperbaric oxygen also has been used. The authors present two interesting patients: 1) A diabetic female with rhinoorbital mucormycosis post total maxillectomy with recurrent mucormycosis and 2) A diabetic female with acute myelogenous leukemia and sphenoid sinus mucormycosis post functional endoscopic sinus surgery with residual mucormycosis. Both patients were receiving Amphotericin B without improvement. Both fungal infections were apparently eradicated with 1/2 strength topical hydrogen peroxide soaks. It appears the hydrogen peroxide destroys mucor and supporting host tissue by oxidation. The authors propose adding 1/2 strength topical hydrogen peroxide soaks to the list of possible adjunctive treatments of mucormycosis.
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PMID:Mucormycosis. Adjunctive therapy with hydrogen peroxide. 881 Aug 81

Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.
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PMID:Vincristine degradation by serum from leukemic patients: role of myeloperoxidase. 883

Myeloperoxidase (MPO) catalyzes a reaction between chloride and hydrogen peroxide to generate hypochlorous acid and other reactive compounds that have been linked to DNA damage. The MPO gene is expressed at high levels in normal myeloid precursors and in acute myeloid leukemias (AMLs) which are clonal derivatives of myeloid precursors that have lost the ability to differentiate into mature blood cells. Two MPO alleles differ at -463 G/A within a cluster of nuclear receptor binding sites in an Alu element. The -463 G creates a stronger SP1 binding site and retinoic acid (RA) response element (RARE) in the allele termed Sp. In this study, we investigate potential links between MPO genotype, MPO expression level, and myeloid leukemia. The SpSp MPO genotype is shown to correlate with increased MPO mRNA levels in primary myeloid leukemia cells. This higher-expressing SpSp genotype is further shown to be overrepresented in acute promyelocytic leukemia-M3 (APL-M3) and AML-M4, suggesting that higher levels of MPO are associated with an increased risk for this subset of leukemias.
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PMID:An allelic association implicates myeloperoxidase in the etiology of acute promyelocytic leukemia. 932 40

Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.
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PMID:Intestinal permeability in patients with acute myeloid leukemia. 982 Jun 31

Inherent resistance of myeloblasts to vincristine (VCR) has been related to the activity of myeloperoxidase (MPO) which can degrade VCR in the presence of hydrogen peroxide (H2O2). We investigated the relationship between VCR degradation and hypochlorous acid (HOCl) generation from the reaction of H2O2 with chlorine (Cl) as catalyzed by MPO. A cell-free system, three human leukemia cell lines (CEM/CCRF, HL-60, U937) and 15 bone marrow samples from children with acute myeloid leukemia (AML) were studied. VCR cytotoxicity was evaluated by MTT assay and by quantitative measurement of apoptosis. In vitro levels of VCR in cell-free systems were measured by high performance liquid chromatography (HPLC), and intracellular HOCl levels by oxidation of 5-thio-2-nitrobenzoic acid with the accompanying decrease in the absorbency at 412 nm. VCR was degraded by increasing concentrations of HOCl in cell-free systems and this activity was inhibited by taurine, which is known to block HOCl activity. This finding was confirmed by the VCR cytotoxicity studies on cell lines. The HOCl-producing myeloblasts from patients were resistant to VCR. In five samples out of eight HOCl was also detected extracellularly. These results suggest that oxidation by HOCl may be the final step in VCR degradation catalyzed by MPO through its action on intracellular H2O2 and Cl. Leukemia (2000) 14, 47-51.
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PMID:Further elucidation of mechanism of resistance to vincristine in myeloid cells: role of hypochlorous acid in degradation of vincristine by myeloperoxidase. 1063 76


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