Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.
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PMID:Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. 142 55

We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation.
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PMID:FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. 184 45

Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed, connected with a pulmonary thrombosis and not with an infective origin. A systematic search for this pathology identified six other children with the same pulmonary complication, five of whom where in the early phase of acute nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow relapse. At the beginning of the symptomatology, all children presented severe hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement. In all patients the arteriography and nuclear imaging studies confirmed the diagnosis. The causes of the thrombi could be connected with neoplastic emboli after cell lysis and/or with the vascular damage resulting from antiblastic therapy. Intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children.
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PMID:Acute respiratory failure and pulmonary thrombosis in leukemic children. 198 61

Plasma and tumor cells from 103 patients with leukemia or lymphoma at initial presentation were investigated for the presence of plasminogen activator inhibitor-2 (PAI-2) antigen, a potent inhibitor of urokinase. PAI-2 was detected in plasma and leukemic cells of the 21 patients with leukemia having a monocytic component [acute myelomonocytic (M4), acute monoblastic (M5), and chronic myelomonocytic leukemias], and in the three patients with acute undifferentiated myeloblastic leukemia (M0). In contrast, this serine protease inhibitor was undetectable in 79 patients with other subtypes of acute myeloid leukemia or other hematological malignancies. Serial serum PAI-2 determinations in 16 patients with acute leukemia at presentation, during therapy, remission, and relapse revealed that in the five patients with M4-M5, elevated PAI-2 levels rapidly normalized under therapy and during remission, but increased again in the patients with a relapse associated with an M4-M5 phenotype. Thus, PAI-2 seems to be a marker highly specific for the active stages of monocytic leukemia, i.e. presentation and relapse. The presence of PAI-2 in the plasma and cells of patients with M0 may give a clue to a monocytic origin of these cells.
Leukemia 1991 Jun
PMID:Plasminogen activator inhibitor-2 in patients with monocytic leukemia. 205 72

In the present study, methotrexate (MTX), was conjugated with a murine monoclonal antibody (79) to human common acute lymphoblastic leukemia antigen (CALLA), with human serum albumin (HSA) as an intermediary. The highest molar ratio of McAb 79:HSA:MTX in the conjugates was 1:2. 63:117. The conjugates obtained retained both antibody binding and drug activities. Although there was some loss of drug activity in binding to antibody, the toxicity of McAb79-HSA-MTX was entirely specific for the target cell, and the cytotoxicity of McAb79-HSA-MTX against CALLA+ cells was greater than that of control S13 (Anti-human urokinase)-HSA-MTX. The ratio of 79-HSA-MTX cytotoxicity to the target and non-target cells was 66:1, whereas there was no cytotoxicity to target cells when McAb79 was used only. There was no cytotoxic difference between 79-HSA-MTX and S13-HSA-MTX against CALLA- SB cells. These results suggest that the cytotoxicity of 79-HSA-MTX against CALLA leukemia cells is specific and this specificity is mediated by McAb79.
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PMID:[Preparation and cytotoxicity of McAb-HSA-MTX conjugates]. 217 64

The K562 leukemia cell line has been extensively used in studies of erythroid differentiation but it has been less well appreciated that treatment of K562 cells with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) leads to loss of their erythroid properties and to acquisition of several megakaryoblastoid characteristics. These include synthesis and surface expression of glycoprotein IIIa, an increase in platelet peroxidase positivity, enhancement of thromboxane A2 receptors, and increased cell volume and DNA ploidy. TPA-treated K562 cells also synthesize and secrete platelet derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), urokinase-plasminogen activator (u-PA) and its specific inhibitor, type 1 plasminogen activator inhibitor (PAI-1). Induction of all these proteins, which have also been found in platelet granules (u-PA on platelet surface receptors) occurs at the level of mRNA accumulation. Therefore, in addition to facilitating studies and cloning of genes specific for erythroid differentiation, the K562 cells offer a tool to approach early steps of megakaryoblast commitment and differentiation. Observations made with the K562 cell line and several other leukemia cell lines co-expressing erythroid and megakaryocyte markers suggest that the erythroid and megakaryocyte lineages diverge from a common bipotent precursor cell.
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PMID:Induced differentiation of K562 leukemia cells: a model for studies of gene expression in early megakaryoblasts. 219 10

Seventy-two consecutive and previously untreated adults with acute non-lymphoblastic leukaemia (ANLL), having a median age of 36 years (range 12 to 71), were prospectively randomised to receive conventional doses of cytosine arabinoside and doxorubicin combined with either etoposide (CTR III) or 6-thioguanine (DAT). Morbidity was comparable between the two regimens and complete remission (CR) rates of 52% and 62% respectively (p greater than 0.50) were not influenced by age above or below 50 years, initial white cell count, French-American-British classification, or race. However, growth pattern in the GM: CFUc assay was found to identify a subgroup of patients who had a significantly higher CR rate. Similarly, the secretion of tissue plasminogen activator by leukaemic blasts in vitro uniformly predicted for primary drug resistance, whereas a CR rate of 68% was associated with production of the urokinase type or a mixture of both enzymes. Remission duration and survival did not differ between these two forms of chemotherapy, nor were they influenced by immunotherapy with C. parvum or the duration of maintenance therapy, whereas age below 50 and the species of plasminogen activator secreted were significant prognostic factors. It is concluded that etoposide can be substituted for 6-thioguanine in these cytosine arabinoside and doxorubicin-containing regimens and that for both combinations the most sensitive prognostic factor for CR and survival is the species of plasminogen activator secreted in vitro by the leukaemic blasts.
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PMID:Chemotherapy of adult acute nonlymphoblastic leukaemia. 220 94

We examined fibrinolytic substances in homogenate of leukemic cells, normal granulocyte or mononuclear cells fraction. Plasminogen activators (PA) were significantly low in normal cells, but they were slightly increased in lymphoblastic leukemia cells and markedly increased in myeloblastic leukemia cells. In almost leukemic cells homogenate, the antigen ratio of tissue type PA (t-PA)/urokinase type PA (u-PA) was about 2.0. In especially AMMoL and AMoL, PA activity had discrepancy between euglobulin lysis time and amidolytic assay using chromogenic substrate. As PA inhibitor (PAI)-II was markedly increased in them. PAI might effect the PA assay. PA activity of leukemic cells homogenate was similar to that without t-PA stimulator and leukemic cells homogenate significantly stimulated t-PA. As both PA activity and antigen were statistically increased in leukemic cells homogenate of patient with disseminated intravascular coagulation (DIC), PA and PA stimulator in leukemic cell might play an important role in hypofibrinogenemia or DIC.
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PMID:[Plasminogen activator in leukemic cell homogenate]. 228 63

The secretion of tissue plasminogen activator (t-PA), urokinase (u-PA) and their inhibitors by the human leukemia cell line K562 was examined. K562 cells normally secrete both t-PA and u-PA in a ratio of 3:1. After addition of 10 or 1 ng/mL phorbol myristate acetate (PMA) to K562 cells, a marked decrease in enzymatic activity is observed in the medium. However, when t-PA antigen rather than activity is measured, an increased amount is found in the medium under these conditions. PMA also induces secretion of the two inhibitors of plasminogen activator: plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). This accounts for the decrease in total enzymatic activity under conditions when production of t-PA antigen is increased. A study of the time course of induction revealed that the synthesis of plasminogen activator occurred before that of its inhibitors. Low concentrations of PMA (0.1 ng/mL) induce t-PA antigen primarily and not the inhibitors. This results in an increase in total enzymatic activity, with 94% of the secreted activity being t-PA. Thus, the secretion of plasminogen activators and their inhibitors can be manipulated in certain leukemic cells by inducers such as PMA.
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PMID:Regulation and secretion of plasminogen activators and their inhibitors in a human leukemic cell line (K562). 250 6

Six human T cell lines HAMA, KUN, KAN, TCL-Haz, TCL-Ter, and TCL-Mor, which were transformed by a retrovirus, human T-cell leukaemia virus (HTLV), constitutively produced plasminogen activators (PAs) in culture supernatants. The amount of PAs produced varied among the cell lines. The PAs were distinguished by immunochemical analysis between two types: urokinase (UK)-type and non-UK-type. KUN, TCL-Ter, and HAMA mainly produced UK-type PA, whereas the other cell lines produced both types. Thus, HTLV-transformed T cell lines differ in the quality and quantity of the PAs they produce. The PAs in the culture supernatants of each cell line were separated into several mol. w forms on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicate that the same cell line produces PAs of different mol. wt. PA production by these cell lines was affected by treatment with phorbol miristate acetate, concanavalin A, and phytohaemagglutinin; the effects were substantially different in each cell line. The data described here indicate that HTLV-transformed T cell lines constitutively produce PAs which are very heterogeneous in both quality and quantity.
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PMID:Production of plasminogen activators by human T-cell leukaemia virus-transformed human T cell lines. 298 92


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