Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human leukemic cell line NB4 was derived from a patient with acute promyelocytic leukemia and is characterized by a specific 15;17 chromosomal translocation. We analyzed the response of NB4 and HL-60 cells to the biomodulators all-transretinoic acid (ATRA), vitamin D3 (Vit D3) and the protein kinase C agonists bryostatin 1 (Bryo 1) and phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). HL-60 cells were used for comparison being arrested at the myeloblastic-promyelocytic stage, but lacking the t(15;17) abnormality. In most experiments Vit D3 was only weakly or not at all effective. The other three reagents effectively slowed or stopped the proliferation of the cells in suspension. Associated with this proliferation arrest was the cell differentiation along the myeloid cell lineages: ATRA modulated morphological features indicative of granulocytic differentiation; Bryo 1 and TPA caused also distinct morphological changes. The inducers up-regulated the expression of CD11b (without changing the surface expression of other markers, e.g. CD13, CD14, CD15, CD33, CD68, HLA-DR) and completely down-regulated the originally strong expression of myeloperoxidase and c-myc at the mRNA level. Thus, ATRA- or protein kinase C activator-induced differentiation involved changes associated with maturational processes. Induction of terminal differentiation of leukemic cells by physiological or pharmacological modulators may be able to control the growth of the malignant cells and has therapeutic implications.
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PMID:Modulation of gene expression in the acute promyelocytic leukemia cell line NB4. 790 56

Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dustlike granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive non-specific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.
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PMID:Acute promyelocytic leukemia: morphological aspects. 809 23

The granule proteins are among the most abundant and characteristic proteins of myeloid cells. They are essential for the antimicrobial activity of these cells and they provide important markers for the differentiation stage of the myeloid series and for the diagnosis of myeloid leukemias. In acute promyelocytic leukemia (APL) there is high production of myeloperoxidase, and its cytochemical detection as well as the t(15;17) chromosomal translocation are important markers in the diagnosis of this acute myelogenous disease. The expression of other granule protein genes in APL has not been systematically determined. We have used the reverse transcriptase-polymerase chain reaction (RT-PCR) method to determine the pattern of expression of granule protein genes at the mRNA level in APL cells. We have examined the expression of the primary granule proteins defensin, myeloperoxidase, elastase, and cathepsin G; the secondary granule proteins lactoferrin, collagenase, and transcobalamin; as well as lysozyme, a protein reportedly found in both primary and secondary granules. mRNAs for all of these granule proteins were present in normal bone marrow mononuclear cells. We found that APL cells from three patients contain, in addition to myeloperoxidase mRNA, mRNAs for elastase, cathepsin G, and lysozyme. One patient had faint but detectable lactoferrin mRNA signal, but collagenase and transcobalamin mRNAs were not detectable in this patient. Defensin mRNA was found in one of the three APL patients, and all the primary granule protein mRNAs measured were found to be expressed in the APL cell line NB4. None of the secondary granule protein mRNAs measured were detectable in NB4 cells. After treatment with retinoic acid (RA), which induces neutrophil maturation of these cells, weak induction of lactoferrin and collagenase but not transcobalamin was observed. However, in view of the weak transcobalamin signal observed in normal bone marrow, the absence of transcobalamin in RA-induced NB4 cells must be interpreted with caution. Interestingly, elastase and cathepsin G mRNA disappeared after RA induction, whereas defensin and myeloperoxidase mRNAs remained present. These findings indicate that granule protein mRNAs are regulated separately and differently, and that only minimal expression of secondary granule protein genes can occur in APL cells.
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PMID:Expression of granule protein mRNAs in acute promyelocytic leukemia. 811 51

Acute promyelocytic leukemia represents 5-10% of acute myeloid leukemia cases (AML) recorded in the literature, occurring more frequently in young adults. It has a special clinical and biological behaviour when compared to the other forms of AML, being characterized by a particular morphology of blast cells (M3 in FAB classification), translocation of chromosomes 15;17, and disseminated intravascular coagulation at diagnosis or after the onset of chemotherapy. Within this AML subgroup there are 2 morphological subsets called the hypergranular promyelocytic leukemia and the hypogranular or variant form. We have studied clinical and laboratory aspects of 19 cases of AML M3 out of 217 AML cases, and observed a high incidence of failure to recognize the M3 variant form, although its diagnosis has been mainly based on cytomorphology. Only 4 out of 8 cases of the variant form received in our laboratory were correctly diagnosed, being the other 4 cases wrongly identified as the myelomonocytic subset of AML (M4). Immunophenotyping with monoclonal antibodies using CD2 and CD7 as T cell markers, CD10 and CD19 as B cell markers and CD33, CD13, CD14, CD15 and anti MPO as myeloid markers is a complementary diagnostic tool that permits solving difficult cases. It is important to classify AML correctly because of the special therapeutic and prognostic features of AML M3, which differently from other AML forms, has been successfully treated with cellular differentiating agents.
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PMID:[M3 variant leukemia: clinical and diagnostic features]. 816 87

Anti-neutrophil cytoplasmic antibodies (ANCA), which are present in Wegener's granulomatosis (WG) and other systemic vasculitis, were detected using the immunoperoxidase method rather than the indirect immunofluorescence method. It was possible to distinguish ANCA patterns (c-ANCA, p-ANCA) by the immunoperoxidase method. When neutrophil smears were treated with 0.4% hydrogen peroxide solution, the endogenous peroxidase activity was sufficiently inhibited. ANCA was also detected, using HL-60 cells (human promyelocytic leukemia) and THP-1 cells (human myelocytic leukemia) as substrates.
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PMID:Detection of anti-neutrophil cytoplasmic antibodies (ANCA) using the immunoperoxidase method. 820 33

We examined the sensitivity of different myeloperoxidase (MPO) detection methods in leukemia cell lines. To this end the MPO-positive acute promyelocytic leukemia cell line NB-4 was diluted into cell populations of the MPO-negative myeloma cell line MM-1 at different ratios. MPO protein was identified by classical cytochemical staining and by a specific anti-MPO monoclonal antibody in an immunofluorescent reaction. Cytochemical staining detected 1% positive cells among 99% negative cells. Careful, but time-consuming observation enabled the detection of positive cells in even higher dilutions. At least a 10-fold increase in sensitivity was achieved with the immunofluorescent method, as brightly fluorescent cells are more amenable for a screening of slides at lower microscopic magnification than the cytochemically visualized cells. MPO mRNA expression was examined in whole cell populations by Northern blotting (maximal sensitivity 1%), a reverse transcriptase-polymerase chain reaction (RT-PCR) amplification assay (sensitivity 0.1%), and by RT-PCR followed by Southern blotting (sensitivity 0.05%). The high sensitivity of PCR-based techniques is offset by the fact that these methods do not allow for the identification and further characterization of the individual, MPO-positive cells. Thus, methods examining bulk populations require homogeneous cell samples in order to avoid false-positivity stemming from a few residual bystander cells. The five different techniques were used to determine the status of MPO expression in 20 randomly chosen leukemia cell lines of myelomonocytic origin. In 11 cell lines (8 positive and 3 negative) all five tests provided concordant results. Three cell lines were Northern-negative, but RT-PCR-positive and MPO protein-positive suggesting that Northern blot analysis is the least sensitive tool. Six cell lines were devoid of MPO protein, at least according to the methods used here, but trace expression of MPO message was documented by PCR. All five techniques have advantages and drawbacks and must be carefully selected in order to obtain useful data. The detection of MPO is of experimental and clinical importance in the distinction of myeloid from lymphoid leukemias, and in the lineage assignment of apparently biphenotypic or unclassifiable cases.
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PMID:Sensitivity of different methods for the detection of myeloperoxidase in leukemia cells. 830 58

The authors describe the functional capabilities of in vivo induced neutrophils from a patient with acute promyelocytic leukemia (French-American-British M3v) treated with differentiation therapy using all-trans-retinoic acid (45 mg.m-2.day-1). The induced neutrophils from the leukemic clone appeared in the blood 7 days after therapy. Normal neutrophils, presumably derived from nonclonal normal hematopoiesis, appeared 15 days after the initiation of therapy. The induced neutrophils were separated from normal neutrophils by density gradient centrifugation. Their origin was established by fluorescence in situ hybridization. The induced neutrophils were morphologically atypical but stained for myeloperoxidase (Sudan black B) and AS-D chloroacetate esterase and were negative for alpha-naphthyl butyrate esterase. Induced neutrophils were functionally mature, showing nitroblue tetrazolium reduction in 72% of the cells compared with 84% in the normal neutrophil fraction. Both the rate and total killing of Staphylococcus aureus (American Type Culture Collection Strain 25923) were normal in both neutrophil fractions. Random locomotion was equivalent and within the normal reference range in both fractions; however, using the under-agarose technique, induced neutrophils showed a minor chemotactic defect in response to both n-formyl-methionyl-leucyl-phenylalanine (score 292, normal 338-868) and complement-derived chemotactic factors (score 420, normal 457-1408). At autopsy, induced neutrophils infiltrated necrotic myocardial tissue, suggesting a normal response to inflammatory stimuli.
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PMID:Functional characteristics of in vivo induced neutrophils after differentiation therapy of acute promyelocytic leukemia with all-trans-retinoic acid. 831 24

We report on a 3 year old girl with acute promyelocytic leukemia (APL) with cerebral infarction due to disseminated intravascular coagulation (DIC) at initial presentation. She was hospitalized because of unconsciousness and petechiae on the chest wall and extremities. Cerebral ischemia and infarction were found on computed tomography scan and magnetic resonance imaging. Peripheral blood content was hemoglobin 7.3 g/dL, white blood cells 1.0 x 10(3) cells/microL (31% blasts) and platelet count was 12 x 10(3) cells/microL. Fragmented erythrocytes were frequently observed on May-Giemsa stained blood smears. Bone marrow aspirates showed normal cellularity, with 60.4% blasts, containing faggot cells. The blasts were positive for peroxidase. Therapy was begun; however, the patient died 1 week after admission.
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PMID:Cerebral infarction in acute promyelocytic leukemia at initial presentation. 877 58

Acute promyelocytic leukemia (APL) is a type of acute leukemia showing unique clinical, morphological and cytogenetic features. A skin infiltration by APL cells is an extremely rare occasion, but there have been several case reports of leukemia cutis in APL, in which all-trans retinoic acid (ATRA) may have induced the skin infiltration. However, no immunohistochemical analyses of the APL cells in the skin have been done to date. A 30-year-old woman with APL developed multiple reddish purple nodules on the extremities in her second complete remission. Histological findings revealed a dense infiltration of medium to large atypical cells, which were positive for myeloperoxidase, throughout the dermis. Despite the conventional chemotherapy and ATRA therapy she died from disseminated intravascular coagulation during her third relapse. Leukemic cells in the peripheral blood before the treatment with ATRA revealed CD3-/CD4-/CD5-/CD7-/CD8-/CD10-/CD13++/CD14-/CD19 -/ CD20-/CD33++/CD38++/CD41-/Ia-, but they expressed CD3-/CD4-/CD5-/CD7++/ CD8-/CD10-/CD13++/CD14-/CD19-/CD20-/CD33++ /CD38++/CD41+/Ia+ after the treatment. We suggest that the alternation of the surface molecules on the tumor cells is closely associated with the skin infiltration of APL cells.
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PMID:Skin infiltration in acute promyelocytic leukemia. 909 68

We established a factor-independent acute myeloid leukemia cell line, designated Ei501. The line has been growing in RPMI 1640 media for 18 months and can be maintained without addition of growth factors. Ei501 is positive for myeloperoxidase and negative for esterase and PAS. Cytogenetic analysis revealed the FAB M3 associated t(15;17) translocation and a translocation of the chromosomes 7 and 8: 46 XX, -7, +t(7;8)(q32;q13), t(15;17)(q22;q12). This karyotype was confirmed by fluorescence in situ hybridization. Ei501 cells express AML-associated surface markers such as CD13, CD33 and CD38. Although 42% of the patient's blast cells were CD34-positive, the line lacks surface expression of CD34. Furthermore the line has a number of characteristics which are detectable in blasts from AML patients, such as surface adhesion molecules, cytokines such as TGF-beta, cytokine receptors such as the IL-2 receptor beta and gamma chains or the IL-4 receptor and the genes for the transcription factor wt-1 (Wilms' tumor gene) and for the proto-oncogene bcl-2, both shown to be present in the majority of patients with AML. Additionally the line can be used as target in cytotoxicity assays using IL-2 activated cytotoxic lymphocytes as effector cells. In conclusion, besides a rare karyotype the Ei501 cell line has several features common in AML, and may therefore be used as a model to study pathogenetic mechanisms in acute myeloid leukemia.
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PMID:Establishment and characterization of a new, factor-independent acute myeloid leukemia line designated Ei501. 918 Feb 96


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