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)

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

We report here a patient with acute lymphoblastic leukemia (ALL) in whom hypofibrinogenemia developed during chemotherapy. The patient was a 65-year-old female who was diagnosed as having common ALL, and she was treated with BHAC-DMPV (enocitabine: 160 mg, daunorubicin : 40 mg, 6-MP: 35 mg, prednisolone (PSL): 60 mg, and vincristine: 2 mg). Hypofibrinogenemia appeared promptly each chemotherapy, including PSL was given. To ascertain a correlation between hypofibrinogenemia and the drugs given in this patient, a trial administration of PSL was attempted during a complete remission state. The level of fibrinogen, in terms of the amount of antigen or coagulability, decreased during PSL treatment, although the levels of AT III, plasminogen, alpha 2PI.Plm complex, and FDP did not change. Thus, it is difficult to speculate that PSL induced destruction of leukemia cells and release of protease from the cells resulting in fibrinolysis and hypofibrinogenemia in this case. These findings also suggest that the administration of only PSL could induce hypofibrinogenemia.
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PMID:[Transient hypofibrinogenemia induced by prednisolone in a case of acute lymphoblastic leukemia]. 268 81

We present the case of a young man with acute monocytic leukemia (French-American-British classification:M5) and systemic hyperfibrinolysis with severe bleeding. Although fibrinolysis is usually mild and secondary to disseminated intravascular coagulation, its role as a primary and dominant factor in rare cases of leukemia warrants that its presence be sought as a cause of abnormal bleeding. Decreased serum plasminogen and increased serum plasmin determined by synthetic substrate assay and a negative protamine paracoagulation test are crucial findings. Use of high-dose epsilon-aminocaproic acid was effective in treating this complication. A transient increase in fibrinolytic activity coincident with the early effect of antileukemic treatment suggested that plasminogen activator and/or fibrinolytic protease substances were released from leukemic cells. Fibrinolytic activity subsequently disappeared with reduction in the population of leukemic cells.
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PMID:Primary fibrinolysis in acute monocytic leukemia. 276 88

Human promyelocytic (HL-60) and monoblast-like (U-937) leukemia cell lines were tested for expression of an endoglycosidase (heparanase) capable of degrading heparan sulfate (HS) side chains in the subendothelial extracellular matrix (ECM). Heparanase activity has been previously shown to be expressed by activated lymphocytes and macrophages and by highly metastatic tumor cells, in correlation with their ability to invade blood vessels and extracellular matrices. Incubation of HL-60 and U-937 cells with sulfate-labeled ECM in the presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) resulted in heparanase-mediated release of heparan sulfate degradation products. This degradation was inhibited by heparin, stimulated by plasminogen and not expressed by cells treated with retinoic acid or dimethylsulfoxide and undergoing neutrophilic differentiation. Heparanase activity was not detected in media conditioned by HL-60 and U-937 cells but was found in their cell lysates, regardless of whether or not the cells were exposed to TPA. These findings imply that TPA-induced differentiation of human myeloid leukemic cells to macrophage-like cells, but not to neutrophilic granulocytes, is associated with expression on the cell surface of a preformed heparanase activity. The enzyme may serve as a marker for human cell differentiation into macrophages, allowing the differentiating cells to traverse the vascular compartment and reach their target sites.
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PMID:Differentiating human leukemia cells express heparanase that degrades heparan sulfate in subendothelial extracellular matrix. 297 42

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

Eleven consecutive leukemia patients with thrombosis induced by asparaginase-prednisone-vincristine therapy were studied to gain insight into the pathogenesis of this complication. Measurement of anti-thrombin III, plasminogen, factor V, and fibrin degradation products as well as platelet aggregation sensitivity to adenosine diphosphate disclosed no consistent abnormalities that would explain pathologic thrombus formation. A decrease in platelet counts observed in nine of 11 patients, prompted us to investigate the possible involvement of factor VIII in this disorder. Levels of factor VIII procoagulant activity, von Willebrand factor (vWF) and ristocetin cofactor were similar to findings for an identically treated comparison group who remained free of thrombotic complications. However, qualitative examination of vWF by crossed immunoelectrophoresis (CIE) revealed a distinct right shift of the immunoprecipitin lines in each of three thrombotic patients tested, whereas a normal profile was found in three similarly treated patients without the complication. This altered pattern had reverted to normal when CIE was repeated 2 to 7 months later. We postulate that the abnormal vWF is related to the development of thrombosis.
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PMID:Altered von Willebrand factor molecule in children with thrombosis following asparaginase-prednisone-vincristine therapy for leukemia. 387 94

Components of the blood fibrinolytic system were measured in 43 patients with leukaemia. Increased fibrinolytic activity, indicated by a reduced plasma plasminogen level, was found in 14 patients. The combination of severe thrombocytopenia and increased fibrinolysis appeared to be a determinant in the production of a haemorrhagic tendency in leukaemia.
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PMID:Fibrinolysis in leukaemia. 524 40

Thirty consecutive patients presenting with acute leukaemia were studied throughout their hospital course to determine if plasma-alpha 2 antiplasmin (P-AP) complexes could be detected during episodes of increased fibrinolytic activity and to correlate this finding with other more conventional laboratory parameters. Increased fibrinolytic activity was a common finding, it was detected in 19 (63%) patients. This was usually present at diagnosis, but occasionally occurred later as a transient phenomenon. Increased fibrinolytic activity could not clearly be associated with either infection or chemotherapy. P-AP complexes were found in 11 (37%) patients and were almost always accompanied by additional laboratory evidence of increased fibrinolysis. These complexes were present in most instances at diagnosis and disappeared following successful chemotherapy. Forty-five per cent of patients with P-AP complexes had low alpha 2-antiplasmin levels and 36% had low plasminogen levels which returned to normal following successful chemotherapy. At diagnosis six of eight patients with P-AP complexes had major haemorrhagic manifestations.
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PMID:Circulating plasmin-antiplasmin complexes in acute leukaemia. 622 73

We have studied the main protease inhibitors of leukocytes, alpha-1-protease (alpha 1-PI), alpha-1-antichymotrypsin (alpha 1-Achy) and alpha-2-macroglobulin (alpha 2-M), as well as different parameters of coagulation and fibrinolysis in 21 cases of acute nonlymphoblastic leukemia (ANLL) before, during and after therapy. Nine of the patients presented signs of DIC, 8 of whom belonged to subtype M3 and to subtype 1 M1. The initial alpha 1-PI and alpha 1-Achy levels, which were elevated, increased during the treatment period. There was no significant difference between patients with and without DIC. However, those leukemic patients with DIC showed a significant decrease in plasminogen (p less than 0.005) and fast antiplasmin (p less than 0.01) only during the treatment compared with DIC free patients. All DIC cases demonstrated circulating plasmin-antiplasmin complex (P-AP) both before and during treatment. Independent of a possible proteolytic action of leukocyte enzymes on clotting factors in the clinical course of ANLL (mainly M3 subtype), our results suggest an activation of plasmin-mediated fibrinolysis related to the activation of plasminogen by leukocytes, reactive DIC or both.
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PMID:Changes in plasma levels of protease and fibrinolytic inhibitors induced by treatment in acute myeloid leukemia. 623 45

Sequential coagulation tests were carried out in 13 children with acute nonlymphoblastic leukemia (ANLL) treated with the German cooperative protocols BFM 78 and 82. The test program included a PTT, Quick's Prothrombin time, Thrombin time, Fibrinogen (Clauss method and RID), coagulation factors II, V, VII, AT III, antiplasmin, plasminogen and FDP. Severe coagulation changes could be demonstrated in ANLL patients with FAB type M2 (myeloblastic leukemia with maturation) and FAB type M5 (monocytic leukemia). Usually they were found already at the time of diagnosis and improved during induction therapy. A variety of coagulation changes were observed, resembling classical DIC, typical hyperfibrinolysis or atypical proteolysis. It is allowed to question the concept of DIC as the typical coagulation disturbance in children with ANLL.
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PMID:[Blood coagulation changes in children with acute myelogenous leukemia: thrombin effect or proteolysis]. 659 Sep 23


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