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)

A differentiation-inducing factor (DIF) for the promyelocytic HL-60 cell line is constitutively produced by the malignant T lymphocyte line HUT-102. DIF was highly purified from HUT-102-conditioned media by means of diethylaminoethanol (DEAE)-chromatography, gel chromatography, and high-resolution, ion-exchange chromatography on a MonoQ column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In addition to inducing differentiation of wild-type HL-60 cells, resulting in secondary inhibition of growth, DIF, at a tenfold lower concentration, inhibited the growth of some clones of the monoblastic U-937 cell line as well as that of subclones of HL-60. The latter effect was most likely a primary growth inhibition and not secondary to differentiation; 50% inhibition of clonogenic growth in agar was seen at approximately 1.0 pmol/L of DIF. In addition, the clonogenic growth of fresh leukemia cells from 10 of 12 patients with acute myeloid leukemia (AML) was inhibited with 50% inhibition at approximately 10 pmol/L of DIF. The growth of normal granulocyte-macrophage colonies was inhibited at a similar concentration, whereas early erythroid colonies were much more resistant. DIF and interferon-gamma (gamma-IFN) were shown to be separate molecules inasmuch as a neutralizing antibody for gamma-IFN did not abolish the DIF effect. The differentiation effect on wild-type HL-60 and the proliferation inhibitory effect on leukemic and normal myeloid cells cochromatographed through all purification steps suggest that both activities are exhibited by identical polypeptides. DIF may have a role in regulating normal hemopoiesis. The growth inhibitory effect of DIF and the ability to induce differentiation of some leukemia cells may suggest a clinical utility in the treatment of leukemia.
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PMID:T lymphocyte-derived differentiation-inducing factor inhibits proliferation of leukemic and normal hemopoietic cells. 349 Aug 86

The expression of a particular alpha-naphthyl acetate esterase isoenzyme which is specific for monocytes was examined in a panel of cultured leukemia-lymphoma cell lines (n = 88), freshly obtained leukemia-lymphoma cells (n = 527), and in fresh (n = 10) and cultured (n = 22) leukemia cells treated with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). The sodium fluoride-sensitive isoenzyme was separated by isoelectric focusing on horizontal thin-layer polyacrylamide gels. The esterase isoenzyme was not detected in untreated or TPA-treated lymphoid, erythroid, or Hodgkin's disease-derived cell lines, but was seen in leukemia cell lines of monocytic origin. TPA induced the new expression of this marker isoenzyme in two leukemia cell lines of promyelocytic and erythroid origin that are known to differentiate along the monocytic-macrophage cell lineage; TPA stimulation increased the staining intensity of the band in monocytoid cell lines. This esterase isoenzyme was found in 92% of the cases classified morphologically as acute myelomonocytic or monocytic leukemia, but only in 3% of the non-monocytic acute myeloid leukemias. All lymphoid or erythroid leukemias or lymphomas were negative. Treatment with TPA of AML and CML cells, which commonly differentiate to monocyte/macrophage-like cells, showed de novo the monocyte-specific isoenzyme. It is concluded that this isoenzyme is a characteristic marker for monocytic leukemia cells and will be a useful tool for the discriminatory identification of the monocytic element in normal and leukemic cells.
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PMID:Occurrence of particular isoenzymes in fresh and cultured leukemia-lymphoma cells. III. Esterase isoenzyme in monocytes. 349 69

An immunoconjugate was prepared containing a disulfide linker between a murine monoclonal antibody (5E9), which recognized the human transferrin receptor, and the ribosome-inactivating protein gelonin. This immunoconjugate was found to consist of two major species, 5E9-gelonin2 and 5E9-gelonin1, and a minor species of 5E9-gelonin3 and less than 10% of either free antibody or gelonin. 5E9-gelonin was extremely toxic in vitro to human tumor cell lines expressing the 5E9 antigen, including a Burkitt's lymphoma, an adult T-cell acute lymphocytic leukemia, an acute myelogenous leukemia, a promyelocytic leukemia, and a cervical carcinoma line. A 24-hour exposure to 10(-9) M immunoconjugate killed 90-99.9% of tumor cells, depending on the cell line. A 5E9-negative murine leukemia was not sensitive to this conjugate. Pharmacokinetic analysis of the disappearance of this immunoconjugate from the murine circulation revealed that it had a biphasic clearance, with an initial rapid phase with a half-life (t1/2) of 3 hours and a later, slower phase with a t1/2 of about 1 day. Analysis of blood samples by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis revealed that a substantial degree of disulfide-linker breakdown occurred in vivo and that the 5E9-gelonin2 species was cleared more rapidly than the 5E9-gelonin1. With use of the same clonogenic assays used to measure in vitro toxicity, biologically active immunoconjugate could be detected in murine plasma for up to 24 hours after iv administration, but the concentration of immunoconjugate by this measure was considerably less than that predicted by SDS-gel electrophoresis. The ability to deliver immunoconjugate to tumor cells in vivo was studied with use of the Burkitt's lymphoma Namalwa as a xenograft in nude mice. It was possible to deliver substantial amounts of immunoconjugate to Namalwa cells in xenografted ascites with direct ip inoculation; lower but significant amounts of immunoconjugate could be delivered to this xenograft after systemic iv administration, provided the tumor burden was low. The 5E9-gelonin conjugate, when administered iv at the time of ip tumor inoculation, prolonged survival of nude mice bearing Namalwa or other human tumors as ascites xenografts and delayed or prevented the growth of subcutaneous nodules of Namalwa in an antigen-specific fashion after a single iv injection. Direct intratumoral administration also inhibited the growth of visible subcutaneous nodules of Namalwa. This immunoconjugate may be useful in the treatment of human cancer.
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PMID:An immunotoxin composed of a monoclonal antitransferrin receptor antibody linked by a disulfide bond to the ribosome-inactivating protein gelonin: potent in vitro and in vivo effects against human tumors. 350 Mar 56

The carboxylic esterase (E.C. 3.1.1.1) isoenzymes from cases of acute myeloid leukemias were separated by analytical isoelectric focusing on horizontal thin-layer gels. One isoenzyme consisting of one or two components (bands) could be completely and selectively inhibited by addition of 40 mM sodium fluoride (NaF) to the staining bath. The 105 cases were classified into the groups M1-M6 according to the FAB proposals. The NaF-sensitive isoenzyme was not detected in cases of FAB groups M1/2 (acute myeloblastic leukemia without or with maturation), group M3 (acute promyelocytic leukemia) or group M6 (erythroleukemia). Thirty-one out of 33 cases in the FAB group M4 (acute myelomonocytic leukemia) and 9/9 cases in FAB group M5 (acute monocytic leukemia) expressed the NaF-sensitive isoenzyme. The NaF-sensitive isoenzyme was found at different staining intensities; all M5 cases showed the isoenzyme at strong or very strong intensity, whereas most of the M4 cases displayed the isoenzyme at weak, medium or strong staining intensity. The data presented are further evidence that the presence of the NaF-sensitive esterase isoenzyme indicates monocytic involvement or differentiation in cases of myeloid leukemias. The easy and fast to perform method of isoelectric focusing can be used to distinguish the monocytic variants among the acute myeloid leukemias and can supplement the morphological analysis of these cases.
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PMID:Expression of a monocyte-specific esterase isoenzyme in cases of acute myeloid leukemias. 386 20

To examine the plasma membrane characteristics of an immature monocytic cell capable of proliferation, we have developed a murine monoclonal antibody that identifies an antigen, Mb1, found on the surface of U-937. In immunofluorescence analyses, Mb1 is not expressed by peripheral blood monocytes (freshly isolated, lymphokine-activated, or cultured for seven days), neutrophils, or any other circulating element. It is also absent on human bone marrow mononuclear cells, including the CFU-GM. Among a series of malignant cells from 50 patients with acute myeloid leukemia (including 22 with monocytic or myelomonocytic leukemia), no Mb1 expression was detected. Continuous human cell lines of B or T cell origin were also negative, as were the myeloid lines HL-60 and K562. Apart from U-937, which uniformly expresses Mb1 in high antigen density, only KG-1 (a myeloblastic line) exhibits Mb1 in low antigen density. Exposure of U-937 to phorbol diester (TPA) under conditions that induce features of macrophage differentiation (including the expression of Mo1) results in a significant reduction in Mb1 expression. Mb1 expression is also reduced as a result of culture of U-937 in medium containing anti-Mb1 antibody (antigenic modulation). On sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radiolabeled immunoprecipitates, Mb1 appears to be a dimeric protein with an estimated molecular weight of 80 kd (43 kd under reducing conditions). Antigenic activity on U-937 is destroyed by treatment with trypsin or papain but is regenerated after 24 hours' culture in enzyme-free medium. Mb1 is a constituent plasma membrane protein of U-937, and its degree of expression relates to the state of cellular differentiation.
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PMID:Mb1, a plasma membrane antigen selectively expressed by U-937 cells. 389 Sep 83

Hyponatraemia was observed in 11 out of 14 consecutive patients with acute myeloid leukaemia and its variants. Metabolic studies on these patients revealed an early increase in the urinary sodium excretion, negative free water clearance, and urine osmolality inappropriately higher than that of the serum. It is postulated that this syndrome is caused by a substance released from the primitive cells of the abnormal myeloid series.
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PMID:Hyponatraemia syndrome in acute myeloid leukaemia. 452 14

A human leukemia-associated differentiation antigen has been identified by a monoclonal antibody (A12) raised to the lymphoblastoid cell line NALM-1. The A12 antigen was expressed on the surface of leukemic cells from patients with common acute lymphoblastic leukemia (c-ALL) as well as on cells of the hematopoietic cell lines NALM-1, Reh-6, Raji, Daudi, CEM, and 8402 as determined by an antibody-binding radioimmunoassay, as well as by indirect immunofluorescence and FACS analysis. This antigen was not detected on normal blood lymphocytes, normal bone-marrow cells or leukemic cells from patients with acute myeloid leukemia (AML). The A12 antigen had an apparent molecular weight of 100 kD as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and appeared to be related to if not identical with the acute lymphoblastic leukemia antigen CALLA described by others. Cross-blocking experiments indicated that preincubation of NALM-1 cells with antibody A12 or J5 (anti-CALLA) could block subsequent binding of 125I-labeled A12 and J5 antibody. These results suggest that the two monoclonal antibodies recognize identical or closely located antigenic sites. The surface membrane expression of A12 antigen in NALM-1 cells was modulated when the cells were cultured in the presence of A12 antibody. Under these conditions, the expression of Ia antigens was unaffected. Re-expression of A12 antigen occurred within 24 h after transfer of the modulated cells into medium devoid of monoclonal antibody.
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PMID:Characterization of a monoclonal antibody (A12) that defines a human acute lymphoblastic leukemia-associated differentiation antigen. 620 73

Alpha-naphthyl acetate esterases (ANAE) were examined by cytochemical and isoelectric focusing (IEF) techniques in 48 cases of acute myeloid leukemia that were classified by conventional morphological criteria. Four main types of ANAE isoenzyme patterns were found by IEF, and comparisons with the expression of membrane receptors (Fc-IgG and C3b) and monocyte-specific antigens (UCHM1, UCHALF, and E11) suggest relationships between ANAE isoenzyme synthesis and distinct myeloid maturational stages. The results further indicate that the blast cells of acute myelomonocytic leukemia (AMML) may represent an immature variant of monocytic leukemia (AMoL) and that morphological examination alone is inadequate in the assessment of monocytic differentiation in acute myeloid leukemias. Inhibition studies of cytochemical ANAE activity with sodium fluoride (NaF) show that the presence of NaF-sensitive or NaF-resistant ANAE enzymes is often unrelated to the diagnostic category of acute leukemia. The results of this study are examined in relation to current concepts of myeloid differentiation, and the application of these findings to the subclassification of acute myeloid leukemias is discussed.
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PMID:Electrophoretic and cytochemical characterization of alpha-naphthyl acetate esterases in acute myeloid leukemia: relationships with membrane receptor and monocyte-specific antigen expression. 623 Jan 19

Surface proteins radiolabeled by lactoperoxidase catalyzed radioiodination and/or sialoglycoproteins tritium-labeled by sodium metaperiodate/NaB3H4 technique, obtained from neoplastic cells of more than 50 patients with malignant hemopoietic disease have been analyzed with acrylamide gradient gel electrophoresis under denaturing conditions (SDS-PAGE). Electrophoretic protein and glycoprotein patterns were essentially similar within the group of examined chronic lymphocytic leukemia (CLL) patients with major surface glycoproteins gp44 and gp29,35. Glycoprotein gp29,35 corresponds by its electrophoretic mobility to Ia-like (HLA-DR antigen), which was identified on some CLL cells also by immunoprecipitation with a conventional anti-Ia antigen serum and subsequent electrophoretic analysis of immuno-precipitated antigen. Electrophoretic patterns of cell surface proteins and glycoproteins of CLL cells were markedly different from those of acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) cells which possessed a characteristic major cell surface glycoprotein gp95 (with relative molecular weight of 95-105k). This glycoprotein was markedly decreased or absent on examined CLL cells. Electrophoretic glycoprotein patterns revealed variations in the expression of several glycoproteins, as well as in the electrophoretic mobility of major glycoprotein gp95 also within the examined groups, particularly in acute myeloblastic leukemia.
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PMID:Cell surface protein and glycoprotein electrophoretic patterns in some human hemopoietic malignancies. 631 39

A membrane antigen with an apparent specificity to B lymphocytes was detected with immunochemical techniques and its properties were analyzed. Anti-B-CLL serum was raised in a rabbit by immunization with B-cell chronic lymphocytic leukemia (B-CLL) cells. This anti-B-CLL serum was absorbed with erythrocytes, liver homogenate and insolubilized immunoglobulins. After further absorption with T-CLL cells, chronic myelocytic leukemia (CML) cells and acute myelocytic leukemia (AML) cells, the anti-B-CLL serum still reacted with peripheral blood B lymphocytes, B-CLL cells and hairy cell leukemia (HCL) cells. In contrast, no reactivity was seen with peripheral blood T lymphocyte or monocytes, or leukemia cells of non-B cell origin. An immunoprecipitation of radiolabeled cell surface proteins was attempted using the anti-B-CLL serum in the presence of Staphylococcus Aureus Cowan 1 (SaCl), and the precipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A membrane antigen with an apparent molecular weight of 76,000 daltons (P-76) was immunoprecipitated with the anti-B-CLL serum from the lysates of normal B lymphocyte, B-CLL cells and HCL cells. The antigen (P-76) is not composed of disulfide-linked subunits and has no structural relationship with HLA-DR (Ia-like) antigens or other known antigens. These results suggest that this antigen is B-lymphocyte specific, and favour the B-lymphocyte nature of HCL cells.
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PMID:A human B lymphocyte antigen (P-76) shared by B-cell chronic lymphocytic leukemia cells and hairy cell leukemia cells. 634 Jul 59


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