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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzyme myeloperoxidase (MPO) is the hallmark of the myeloid lineage. We have analysed the presence of MPO in blasts from 180 cases of acute leukaemia (103 acute myeloid leukaemia (AML) and 77 acute lymphoid leukaemia (ALL) by means of monoclonal antibodies anti-MPO and immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase method). The aim of the study was to investigate the specificity and sensitivity of this marker compared with MPO cytochemistry by light (LM) and electron microscopy (EM), and with the expression of myeloid antigens. Anti-MPO was positive (greater than 3% blasts) in all but one of the 90 AML positive by LM cytochemistry. Of 13 AML cases negative by MPO cytochemistry, six showed 3-10% blasts reactive with anti-MPO and were also positive with antibodies to CD13 and/or CD33. The presence of MPO was confirmed in four of these by EM. The overall positivity of anti-MPO in AML was 92%. Anti-MPO was negative in all but two ALL (6% and 8% positive blasts). The blasts in these two cases were also CD13, CD33 and MPO positive by EM; both were thus reclassified as biphenotypic. Another two ALL reinterpreted as biphenotypic were negative by MPO cytochemistry and anti-MPO but were MPO positive by EM and with CD13 and/or CD33. We conclude that anti-MPO is a sensitive and specific early marker of myeloid blasts and should be incorporated in the routine immunophenotyping of acute leukaemia.
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PMID:The role of an anti-myeloperoxidase antibody in the diagnosis and classification of acute leukaemia: a comparison with light and electron microscopy cytochemistry. 131 Nov 96

We herein describe an unusual case of acute myeloid leukaemia (AML) showing strong cytochemical reactivity for myeloperoxidase (MPO) but surprisingly no reactivity using flow cytometry for any of the lineage-specific cell surface markers, i.e. myelomonocytic antigens CD13, CD14 and CD33; or B-lymphoid antigens CD19, CD20 and immunoglobulins; or T-lymphoid antigens CD2, CD3 and CD5. The strong reactivity for MPO and the complete absence of reactivity for CD13 and CD14 was verified by an independent assay involving alkaline phosphatase-anti-alkaline phosphatase (APAAP). Our case is of interest for at least two reasons: First, a poorly differentiated variant of AML (negative for MPO but positive for one or more of the myeloid-lineage CD antigens) has been designated FAB M0. In terms of the expression of phenotypic markers, our case may be considered as an 'MPO (+), CD antigen (-) AML'. The CD antigens are known to be expressed very early during myeloid differentiation whereas MPO (in its functional form) is viewed as being expressed relatively late in the process. It is therefore intriguing from a biological standpoint why the supposedly early antigens (CD33 and CD13) remain unexpressed; this may represent an example of 'asynchronous differentiation' in leukaemia. Second, from a practical standpoint, the use of immunophenotyping as a first-line diagnosis would fail to detect such cases. This case strengthens the notion that immunophenotyping by flow cytometry does not eliminate the necessity of performing peroxidase cytochemical staining.
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PMID:Acute myeloid leukaemia with an unusual phenotype: myeloperoxidase (+), CD13 (-), CD14 (-) and CD33 (-). 138 46

Immunophenotypic analysis of acute leukemias is time consuming and often requires flow cytometric analysis. A 1-hour alkaline phosphatase-labeled streptavidin-biotin immunocytochemical procedure was evaluated as an alternative. Seventeen cases of acute leukemia, including 10 acute lymphocytic (ALL) and 7 acute nonlymphocytic, were phenotyped by the rapid immunocytochemical procedure and the results were compared with standard analyses. In all 17 cases, the diagnoses made using standard cytochemical and immunologic methods were the same as obtained in blinded reviews by rapid immunocytochemical analysis. Nine cases of precursor B-cell ALL were positive for CD19 and/or CD22. Five CD19 + cases of ALL reacted with anti-myeloperoxidase, with one case also positive for CD15. CD15 positivity was confirmed on repeated study as well as with plastic section immunoperoxidase staining. Nine cases of ALL were positive for CD10 and eight were positive for terminal deoxynucleotidyl transferase. One case of ALL marked as T-cell ALL with CD1, CD2, CD3, and CD7. All cases of acute nonlymphocytic leukemia were positive for CD15, CD13, and/or CD33; anti-myeloperoxidase was positive in all but one case of monocytic leukemia. All cases of acute nonlymphocytic leukemia were negative for CD10 and one was positive for terminal deoxynucleotidyl transferase. Acute leukemias apparently may be phenotyped easily and accurately in 1 hour with this immunocytochemical technique, and slides may be stored permanently for review. There was in these 17 cases high correlation of the diagnoses with standard flow cytometric and cytochemical results. This rapid method allows a coordinated evaluation of morphologic features and immunophenotype; the latter features facilitated confirmation of unexpected reactivity of myeloid markers CD15 and MPO-7 in some cases of ALL.
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PMID:Rapid immunocytochemical analysis of acute leukemias. 159 10

Cell surface antigen expression during proliferation and differentiation of human erythroid progenitors was examined using a combination of sequential micromanipulations of paired daughter cells derived from erythroid burst-forming units (BFU-E) and immuno-staining with a panel of monoclonal antibodies. Single hematopoietic progenitors were identified in methylcellulose cultures containing human cord blood mononuclear cells and micromanipulated individually to secondary culture. Paired daughter cells, granddaughter cells, and subsequent generations, whose counterparts produced erythroid bursts, were stained with various cytochemical and immuno-alkaline phosphatase stainings. Most paired daughter cells of BFU-E immunostained positively with anti-platelet glycoprotein(GP) IIb, antiplatelet GPIIb/IIIa, anti-HLA-DR, and antitransferrin receptor antibodies. Acid phosphatase staining was also positive. Neither CD34 nor CD33 antigens were identified on the cells. CD36 and blood group A antigens were first identified on cells from aggregates containing 32 to 64 cells after 4 days of secondary culture and preceded the expression of glycophorin A and hemoglobin alpha. These results indicate that various cell surface antigens were sequentially expressed during the proliferation and differentiation of erythroid progenitors, and that our procedure may be useful for clarifying the morphologic and immunologic properties of hematopoietic stem cells.
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PMID:Changes in cell surface antigen expressions during proliferation and differentiation of human erythroid progenitors. 163 21

Eight cases of acute myelogenous leukemia with (8; 21) translocation were reported. As recently reported, they showed following features: M2 morphology in FAB classification (all 8 patients), abnormal granulocyte maturation, i.e. large granules and pseudo Pelger-Huet forms (5), Auer rods (8), occasional eosinophilia (2), frequent loss of one sex chromosome (5), the low neutrophil alkaline phosphatase activity (5), and tumor formation (one). Both CD13 and CD33 antigens were expressed on smaller number of leukemic cells than the other AML (M2) cells, whereas CD34 and HLA-DR antigens were expressed on higher number of cells. Interestingly CD19 antigen was detected on a small to large population of tumor cells from four out of six patients. Despite the high remission rate, many of them relapsed within one year. More intensive postinduction and maintenance therapy should be considered for those patients.
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PMID:[Clinical and cytological features of acute myelogenous leukemia with 8; 21 chromosome translocation]. 192 Aug 38

A 34-year-old man was admitted with lumbago and anemia in November 1992. Hematological examination revealed an Hb 9.2g/dl, WBC count 13,500 microliters (33% blasts), and monocyte count 3,400/microliters. Bone marrow examination showed hyperplasia with dysplasia in trilineage blood cells and increased blasts (21.8%). A diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T) was made. Cytochemical examination revealed the neutrophils in the peripheral blood were 66.5% positive for alpha-naphthyl butyrate esterase inhibited by sodium fluoride, 4.0% positive for peroxidase and 75% positive for alkaline phosphatase. The results of immuno-alkaline phosphatase stainings (avidin biotin alkaline phosphatase complex method) of neutrophils were as follows; CD16 (94.5%), CD24 (91.0%), CD13 (93.0%), CD14 (52.5%), CD33 (39.0%), CD36 (16.5%), HLA-DR (17.0%). These neutrophils exhibited monocyte-specific features and failed to show characteristics of neutrophils.
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PMID:[CD14-positive and nonspecific esterase-positive neutrophils in a patient with refractory anemia with excess of blasts in transformation]. 750 51

Expression of P-glycoprotein (PGP), the product of the multi-drug resistance mdr1 gene was studied by immunocytochemistry on bone marrow slides using JSB1 monoclonal antibody and the alkaline phosphatase-antialkaline phosphatase (APAAP) and avidin-biotin-peroxidase (ABC) techniques in 82 cases of untreated myelodysplastic syndromes (MDS), of whom ten had evolved to AML (MDS-AML). The relationship between PGP expression, myeloperoxidase activity and immunophenotype of blast cells, karyotype and outcome was also analyzed. PGP expression was found in the blasts of 34 of the 82 patients (41%), the majority of blasts being stained in positive cases. PGP positivity was rare in 'low risk' MDS (RA and RARS: 2/12 cases) as opposed to 'high risk' MDS (RAEB, RAEB-T, CMML: 25/60 cases) and MDS-AML (7/10 cases) (p = 0.04). PGP expression was positively correlated to the presence of myeloperoxidase activity in less than 3% of blasts (p = 0.025), and CD34 antigen expression (p = 0.04), whereas CD33 antigen expression had borderline significance (p = 0.07), demonstrating that PGP expression predominated in blasts with an immature phenotype. An abnormal karyotype, and especially the presence of monosomy 7, was not correlated to a higher incidence of PGP expression, however. There was a trend for more frequent progression to AML and for shorter survival in PGP-positive cases, but differences with PGP-negative cases were not significant. Twenty patients received intensive anthracycline-Ara-C chemotherapy and ten (50%) achieved complete response, including 9/13 (69%) PGP-negative cases and 1/7 (14%) PGP-positive cases (p = 0.03). Twenty other patients were treated with low-dose Ara-C and ten (50%) responded (complete or partial response). PGP-positivity did not negatively affect response to low-dose Ara-C: 4/11 responses in PGP-negative, and 6/9 responses in PGP-positive patients (p = 0.18). Because the treatment choice in advanced MDS (especially between anthracycline-Ara-C or low-dose Ara-C, chemotherapy) is difficult, our preliminary therapeutic results suggest that the analysis of PGP expression could have practical importance in MDS. These findings however, will have to be confirmed on larger numbers of patients. Clinical trials using drugs potentially reverting mdr, activity could also be warranted in MDS.
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PMID:Expression of the multidrug resistance P-glycoprotein and its relationship to hematological characteristics and response to treatment in myelodysplastic syndromes. 751 32

We investigated the phenotypes of blast cells of 53 patients with acute leukemia by a modified streptavidin-biotin alkaline phosphatase (SAB-AP) labeling technique, using a panel of monoclonal antibodies [MoAb; anti-CD11b, CD13, CD14, CD33, CD34, CD41, CD3, CD7, CD10, CD19, anti-HLA-DR, and anti-myeloperoxidase (MPO)]. The selection of an optimal fixative solution for each antigen from five options of various combinations of formalin, acetone, methanol, and/or ethanol, successfully conserved cell morphology and improved specific reaction compared with the conventional methods which used a single fixative for multiple antigens. We compared the SAB-AP results with those obtained by flow cytometry (FCM) for surface markers in each case. High concordance rates for both positive and negative results were observed for each marker. However, positive reaction for some markers (anti-CD13, CD14, CD33, and CD34) were often noted only in the cytoplasm by the SAB-AP method, indicating that combination of these two methods is essential for the precise immunophenotyping of poorly differentiated leukemia cells.
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PMID:Usefulness of immunocytochemistry for phenotypical analysis of acute leukemia; improved fixation procedure and comparative study with flow cytometry. 771 39

Leukemic transformation in essential thrombocythemia (ET) is rare. We describe a patient with ET which transformed to megakaryoblastic leukemia with myelofibrosis after treatment with melphalan for 8 years. His course after transformation smouldered for 20 months without antileukemic chemotherapy. A 61-year-old man was referred by a local doctor to Niigata University Hospital due to nasal bleeding in June 1984. Complete blood count (CBC) was as follows; hemoglobin 12.4 g/dl, platelets 268.8 x 10(4)/microliters, and white blood cells 11,900/microliters, with differentials of 39% PMN, 1% basophils, 2% eosinophils, 4% monocytes, and 13% lymphocytes. Bone marrow examination revealed hyperplasia of megakaryocytes without increase of reticulin fibers. Neutrophil alkaline phosphatase activity and karyotype of marrow cells were normal. ET was diagnosed. He was followed up by local doctor. The platelet count was controlled at a level of approximately 40 x 10(4)/microliters with melphalan for eight years. In January 1992 he developed pain in his lower extremities. He was admitted to our hospital on May 29, 1992. CBC was as follows; hemoglobin 8.9 g/dl, platelets 14.3 x 10(4)/microliters, and white blood cells 3,500/microliters, with differentials of 25% PMN, 5% monocytes, 28% lymphocytes, and 24% blasts. Bone marrow aspiration was unsuccessful and bone marrow biopsy revealed increases in fibroblasts and collagen fibers. Circulating blasts were positive for CD4, CD7, CD25, CD13, CD33, CD34, and HLA-DR and partly positive for CD41 and CD36. In ultrastructural cytochemistry blasts were positive for platelet peroxidase but negative for myeloperoxidase. Cytogenetic study revealed 46, XY, +der (1) t(1:7) (p11;q11) in all of five metaphases. He was diagnosed with megakaryoblastic leukemia accompanied by myelofibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Essential thrombocythemia in transformation to smouldering megakaryoblastic leukemia with myelofibrosis]. 853 33

All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.
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PMID:AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. 860 43


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