Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 30-year-old man with a diagnosis of acute promyelocytic leukemia (APL) was admitted. Laboratory findings were as follows: WBC 32,900/microliter with 88% promyelocytes, Hb 10.4 g/dl, platelets 2.6 x 10(4)/microliter. Coagulation tests revealed DIC. Bone marrow was hypercellular with 91.8% promyelocytes which were strongly positive for peroxidase and positive for alpha-naphthyl butyrate esterase. Cytogenetic study revealed 46, XY, t(15;17) (q22:q11). He was treated with all-trans retinoic acid (ATRA) along with hydroxyurea (HU) and low-molecular weight heparin (LMH). Because his WBC increased to 93,700/microliter on day 6 of ATRA therapy, DCMP chemotherapy was given, while ATRA was withheld. He developed enterocolitis due to myelosuppression. ATRA was restarted along with granulocyte-colony stimulating factor (G-CSF). His WBC rose to 10,400/microliter with a marked, but temporary predominance of myelomonocytes both in peripheral blood and in bone marrow. These myelomonocytoid cells were positive for specific and nonspecific esterase double stainings. Then he entered complete remission. It was of interest that myelomonocytoid differentiation of APL cells was induced by ATRA. The etiology was discussed.
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PMID:[All-trans retinoic acid-induced myelomonocytoid differentiation in acute promyelocytic leukemia]. 919 90

From a series of 176 patients with acute myeloid leukemia (AML), we have identified 11 patients with HLA-DR-negative AML excluding acute promyelocytic leukemia. All patients showed not (15; 17) or consistent chromosomal abnormalities. According to the French-British-American criteria, seven, three, and one patients were classified into M1, M2, and M4, respectively. Blasts from these patients were CD33+, HLA-DR-, and lymphoid-antigen-. All patients entered complete remission after induction therapy. Of these, blasts from four patients had strikingly invaginated nuclear membrane and finely granular peroxidase activity. The phenotype of the blasts was CD33+, CD34-, CD2-, and HLA-DR-. All four patients showed hyperleukocytosis on initial presentation. One patient received all-trans retinoic acid at relapse, however, the drug did not induce the differentiation of the blasts. These four patients were suspected to have acute myeloid/natural killer (NK) leukemia because of the prominent morphological feature of the blasts and the initial hyperleukocytosis, although NK cell activity of the blasts was not examined. Since HLA-DR-negative AML is heterogeneous, it is necessary for identifying acute myeloid/ NK leukemia within the disorder.
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PMID:[Clinicopathological features in HLA-DR-negative acute myeloid leukemia]. 931 Dec 67

We recently established an acute promyelocytic leukemia (APL) cell line (HT93) that has the capacity to differentiate into neutrophils and eosinophils in response to all-trans retinoic acid (ATRA) and human hematopoietic cytokines. The cells had a myeloblastic morphology, were positive for surface CD33, CD34, and CD56, and showed the following karyotypes: 46, XY, t(1;12)(q25;p13), 2q+, t(4;6)(q12;q13), and t(15;17)(q22;q11). When the cells were cultured with ATRA, they showed nuclear segmentation and developed secondary granules consisting in part of neutrophils and eosinophils. In the presence of ATRA and granulocyte colony-stimulating factor (G-CSF), the cells showed polymorphonuclear neutrophil differentiation accompanied by expression of surface CD11b, CD15, CD10, positive activity for neutrophil alkaline phosphatase (NAP), and NAP mRNA expression. In cultures with ATRA and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL (interleukin)-3, or IL-5, HT93 showed remarkable eosinophil maturation at day 8 as determined by luxol fast blue staining, in addition to expression of eosinophil peroxidase and major basic protein. These results indicate that HT93 is an APL cell line with the ability to differentiate into neutrophils and eosinophils, and that these lineages are dependent on the CSF added. HT 93 should prove to be a useful model in analyzing the effects of hematopoietic cytokines on proliferation, differentiation, and maturation of hematopoietic progenitors.
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PMID:Hematopoietic cytokine-dependent differentiation to eosinophils and neutrophils in a newly established acute promyelocytic leukemia cell line with t(15;17). 947 3

Acute promyelocytic leukemia (APL), defined by the French-American-British (FAB) classification as the M3 subtype of acute myeloblastic leukemia (AML), is readily diagnosed by direct cytomorphologic examination. The potential difficulty in recognizing the microgranular variant of APL (M3v) stems from the morphological characteristics of APL leukemic cells, which resemble monocytes. From 109 newly diagnosed acute leukemic patients, 48 were classified as AML and 16 of these patients (33%) had APL Mononuclear cells (MNC) of all APL patients were analyzed by flow cytometry for immunophenotypic features and forward and right angle scatter (FW-SC/RT-SC) light characteristics. Two clearly different FW-SC/RT-SC distribution patterns were recognized and defined as hypergranular (mature cells) and hypogranular (immature cells). Correlation between FW-SC/RT-SC patterns and the FAB system was poor: from eight patients classified as M3, six had the hypergranular pattern and two had the hypogranular pattern; from eight cases with M3, five and three patients had hypogranular and hypergranular patterns, respectively. The most relevant cellular immunophenotypic feature was the high frequency of CD34+ cases (5/7) recorded exclusively in patients with the hypogranular pattern. An interesting finding was that MNCs of all APL patients changed color from beige to green in the course of 3-4 h, whereas none of the 93 specimens of non-M3 acute leukemia cases showed this phenomenon. Summarizing, the FW-SC/RT-SC characteristics of APL blast cells along with the immunophenotype may represent an objective and reproducible measurement system to distinguish microgranular (M3v) from typical (M3) APL In addition, the present study has identified another unique feature of APL based on the green color of their blast cells imparted by the high content in myeloperoxidase.
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PMID:Light scatter and immunophenotypic characteristics of blast cells in typical acute promyelocytic leukemia and its variant. 970 97

We report the first Japanese case of acute promyelocytic leukemia with t(11;17)(q23;q21) and CD56. A 41-year-old man with schizophrenia was hospitalized because of the appearance of blasts with Auer bodies in his peripheral blood. A bone marrow smear showed an abundance of abnormal cells with scanty azurophile granules in the cytoplasm and somewhat lobulated nuclei. Because the abnormal cells demonstrated strongly positive peroxidase reactivity with a few faggot bodies, the patient was given a diagnosis of acute promyelocytic leukemia (M3v according to the FAB classification). However, chromosome analysis revealed t(11;17)(23; q21). All-trans retinoic acid (ATRA) was not effective. Mitoxantrone was more effective than daunorubicin, and resulted in a complete remission with a normal karyotype. About 9 months later, the patient suffered a relapse. Surface marker analysis demonstrated blasts that were positive for CD56, CD13, and CD33. MEC (mitoxantrone, etoposide, cytarabine) therapy was ineffective. Although ATRA was administered at a dose of 80 mg/day for more than 2 months, the number of myelocytes and promyelocytes increased Finally CAG (cytarabine, aclarubicin, G-CSF) therapy was initiated, but the patient died due to intracranial invasion and hemorrhage accompanied by disseminated intravascular coagulation.
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PMID:[Acute promyelocytic leukemia with t(11;17)(q23;q21)]. 1019 5

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit carcinogen-induced preneoplastic lesion formation in mouse mammary organ culture and tumorigenesis in the two-stage mouse skin model. Cancer chemopreventive potential was also suggested in various assays reflective of the three major stages of carcinogenesis. Anti-initiation activity was indicated by its antioxidant and antimutagenic effects, inhibition of the hydroperoxidase function of cyclooxygenase (COX), and induction of phase II drug-metabolizing enzymes. Antipromotion activity was indicated by antiinflammatory effects, inhibition of production of arachidonic acid metabolites catalyzed by either COX-1 or COX-2, and chemical carcinogen-induced neoplastic transformation of mouse embryo fibroblasts. Antiprogression activity was demonstrated by its ability to induce human promyelocytic leukemia (HL-60) cell differentiation. Moreover, pretreatment of mouse skin with resveratrol significantly counteracted 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress, as evidenced by numerous biochemical responses. Resveratrol reduced the generation of hydrogen peroxide, and normalized levels of myeloperoxidase and oxidized-glutathione reductase activities. It also restored glutathione levels and superoxide dismutase activity. As judged by the reverse transcriptase-polymerase chain reaction, resveratrol selectively inhibited TPA-induced expression of c-fos and transforming growth factor-beta 1 (TGF-beta 1), but did not affect other TPA-induced gene products including COX-1, COX-2, c-myc, c-jun, and tumor necrosis factor-alpha. These data indicate that resveratrol may interfere with reactive oxidant pathways and/or modulate the expression of c-fos and TGF-beta 1 to inhibit tumorigenesis in mouse skin. As reported herein, in addition to the activities described above, resveratrol inhibited the de novo formation of inducible nitric oxide synthase (iNOS) in mouse macrophages stimulated with lipopolysaccharide. This finding suggests an additional mechanism by which resveratrol may function as a cancer chemopreventive agent.
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PMID:Cancer chemopreventive activity of resveratrol. 1037 Aug 67

We describe an 8 year old boy who had received chemotherapy for an acute promyelocytic leukemia and developed a secondary leukemia 27 months after the diagnosis of this first malignancy. Blasts cells were positive for cytoplasmic markers CD22, CD3 and myeloperoxidase. Cell surface T and myeloid-associated markers were also detected. Cytogenetic study disclosed monosomy 7. The patient achieved complete remission, but relapsed 15 months later with identical immunophenotypic and cytogenetic findings. Three-lineage commitment is proved by the expression of specific criteria for myeloid, and lymphoid T and B typing. A multipotent immature progenitor must be the target of leukemogenic agents. The prognosis is obviously ominous.
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PMID:Acute trilineage leukemia with monosomy of chromosome 7 following an acute promyelocytic leukemia. 1043 80

We examined the mechanism of H(2)O(2)-induced cytotoxicity and its relationship to oxidation in human leukemia cells. The HL-60 promyelocytic leukemia cell line was sensitive to H(2)O(2), and at concentrations up to about 20-25 micrometer, the killing was mediated by apoptosis. There was limited evidence of lipid peroxidation, suggesting that the effects of H(2)O(2) do not involve hydroxyl radical. When HL-60 cells were exposed to H(2)O(2) in the presence of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we detected a 12-line electron paramagnetic resonance spectrum assigned to the POBN/POBN(.) N-centered spin adduct previously described in peroxidase-containing cell-free systems. Generation of this radical by HL-60 cells had the same H(2)O(2) concentration dependence as initiation of apoptosis. In contrast, studies with the K562 human erythroleukemia cell line, which is often used for comparison with the HL-60, and with high passaged HL-60 cells (spent HL-60) studied under the same conditions failed to generate POBN(.). Cellular levels of antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase did not explain the differences between these cell lines. Interestingly, the K562 and spent HL-60 cells, which did not generate the radical, also failed to undergo H(2)O(2)-induced apoptosis. Based on this we reasoned that the difference in H(2)O(2)-induced apoptosis might be due to the enzyme myeloperoxidase. Only the apoptosis-manifesting HL-60 cells contained appreciable immunoreactive protein or enzymatic activity of this cellular enzyme. When HL-60 cells were incubated with methimazole or 4-aminobenzoic acid hydrazide, which are inhibitors of myeloperoxidase, they no longer underwent H(2)O(2)-induced apoptosis. Hypochlorous acid stimulated apoptosis in both HL-60 and spent HL-60 cells, indicating that another oxidant generated by myeloperoxidase induces apoptosis and that it may be the direct mediator of H(2)O(2)-induced apoptosis. Taken together these observations indicate that H(2)O(2)-induced apoptosis in the HL-60 human leukemia cell is mediated by myeloperoxidase and is linked to a non-Fenton oxidative event marked by POBN(.).
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PMID:Myeloperoxidase is involved in H2O2-induced apoptosis of HL-60 human leukemia cells. 1080 11

The benzene metabolite hydroquinone (HQ) is postulated to exert its myelotoxicity by bioactivation to reactive quinone derivatives in myeloperoxidase (MPO)-containing cells. In this study, the role of caspases in hydroquinone-induced apoptosis in MPO-rich HL-60 promyelocytic leukemia and MPO-deficient Jurkat T-lymphoblastic leukemia cells was investigated. HQ-induced apoptosis in both cell types was accompanied by phosphatidylserine (PS) exposure, caspases-3/-7 activation, PARP cleavage, DNA fragmentation, and ultrastructural changes as assessed by electron microscopy. In HL-60 cells, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) blocked activation of caspases-3/-7, cleavage of PARP, and DNA, but PS externalization and cytoplasmic changes were not significantly affected. In marked contrast, all features of apoptosis were completely inhibited by Z-VAD.FMK in HQ-treated Jurkat cells. These data provide evidence for Z-VAD.FMK-insensitive and caspases-3/-7-independent pathway(s) in the externalization of PS and cytoplasmic changes during HQ-induced apoptosis in HL-60 cells. In contrast, in Jurkat cells, all of these changes required caspase activation. The ability of HQ to induce equivalent apoptosis in both MPO-deficient Jurkat cells and MPO-rich HL-60 cells demonstrates that MPO-catalyzed bioactivation of HQ is not a prerequisite for toxicity. The differential mechanisms of apoptosis in HL-60 and Jurkat T cells may reflect the MPO activity of these cells and, as a result, the amount of reactive BQ and other metabolites that are generated.
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PMID:Differential involvement of caspases in hydroquinone-induced apoptosis in human leukemic hl-60 and jurkat cells. 1154 41

Recently, considerable attention is focused on anti-carcinogenic phytochemicals, particularly those derived from medicinal or edible plants. [6]-Paradol, a pungent phenolic compound present in certain Zingiberaceae plants, is known to have antimicrobial and analgesic activities. The compound has been reported to attenuate promotion of skin carcinogenesis and TPA-induced ear edema in female ICR mice, and to induce apoptosis in cultured human promyelocytic leukemia (HL-60) cells. In this study, we performed several biochemical studies to evaluate and compare the cancer chemopreventive potential of [6]-paradol and its synthetic derivatives. [6]-Paradol and its synthetic nonpungent analog, [6]-dehydroparadol significantly decreased the incidence and the multiplicity of skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application of [6]-paradol and its derivatives inhibited TPA-induced ear edema and H(2)O(2) production and myeloperoxidase activity in the dorsal skin of mice. Induction of TPA-induced mouse epidermal ornithine decarboxylase (ODC) activity and H(2)O(2)- and UV-induced formation of oxidized DNA bases in vitro were also attenuated by the above compounds. These results indicate that [6]-paradol and its derivatives possess the cancer chemopreventive potential.
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PMID:Antioxidative and antitumor promoting effects of [6]-paradol and its homologs. 1155 96


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