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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expressions of thrombomodulin (TM) and tissue factor (TF) by all-trans retinoic acid (ATRA) were studied in human leukemic cell lines including NB4 (acute promyelocytic leukemia) and U937 (monoblastic leukemia). ATRA remarkably upregulated TM antigen expression in cell lysates as well as TM cofactor activity on the cell surfaces of NB4. The level of TM mRNA in NB4 cells was increased by ATRA. Inherently procoagulant NB4 cells contained markedly higher content of TF, which was efficiently reduced by ATRA. Modest increase of TM and decrease of TF were observed when NB4 cells were treated with dibutyryl cyclic adenosine monophosphate (dbcAMP). On the other hand, both ATRA and dbcAMP showed dramatic increase of TM antigen level and modest decrease of TF antigen in U937 cells. These results suggest that ATRA regulates expressions of TM and TF antigens and activity in NB4 and U937 cell lines, and provide evidence for a potential efficiency of ATRA as a preventive and therapeutic agent for disseminated intravascular coagulation in promyelocytic and monocytic leukemia.
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PMID:All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells. 794 72

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well-known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre-B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients.
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PMID:Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: leukemic cell procoagulant activity is not responsible for the hypercoagulable state. 796 91

Monocytes/macrophages and endothelial cells express tissue factor (TF), an initiator for blood clotting pathway, following their activation accompanied by immune response and/or inflammation. This TF expression results in thrombin generation and fibrin formation around these cells and possibly participates in host-defense mechanism. TF expression by these cells is also a risk-factor to vascular diseases including arteriosclerosis and thrombosis. In cancer and leukemia patients elevation of their plasma TF level associated with DIC and related coagulation disorders.
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PMID:[Current scopes on tissue factor: its physiological function and relationship with coagulation diseases]. 802 93

In 43 patients with leukemia, we determined the increase of tissue factor (TF) activity production by leukemic cells that was induced by incubation with endotoxin at the time of admission. Definite disseminated intravascular coagulation (DIC) developed in 8 patients on admission (Group III) and in 8 patients just after the initiation of treatment (Group II), but not in the remaining 27 patients (Group I). TF activity before incubation (TF1) was 0.70 U/10(8) cells or more in 6 patients of Group III, while it was less in all the patients of Group II and 25 of the 27 patients of Group I. On the other hand, TF activity after incubation with endotoxin (TF2) increased to more than 1.11 U/10(8) cells in all the patients of Groups II and III, while it remained less in all the patients of Group I. These results suggest that the leukemic cells in Group II might not have expressed sufficient TF activity to cause DIC until chemotherapy was begun, and that 1.11 U/10(8) cells or more of TF2 might strongly indicate the development of DIC during treatment for leukemia.
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PMID:Prediction of disseminated intravascular coagulation in patients with leukemia. 806 87

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.
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PMID:Increased plasma level of interleukin-6 in disseminated intravascular coagulation. 821 55

Acute promyelocytic leukemia (APL) cells express different types of procoagulant activity (PCA), including tissue factor (TF), and cancer procoagulant (CP). The aim of this study was to investigate whether the NB4 cell line, the first ever isolated human APL line, with the typical t(15;17) chromosomal balance translocation, possess CP as well as the cells freshly isolated from APL patients. Secondly, since the NB4 line is maturation inducible by all-trans-retinoic acid (ATRA), we wanted to verify whether CP, if present, was affected by ATRA treatment. The NB4 cells were able to shorten the recalcification assay of normal human plasma (total PCA). To distinguish CP in the assay for clotting activity, two criteria were used, the independence from factor VII to trigger blood coagulation and the sensitivity to cysteine proteinase inhibitors. Forty-seven per cent of total PCA of cell extracts was found to be FVII-independent PCA. A similar proportion of FVII-independent activity (42%) was detected in the cell serum-free supernatants. The activity was significantly decreased by cysteine proteinase inhibitors, including HgCl2, lodoacetic acid and Z-Ala-AlaCHN2. Additionally CP was directly identified and quantified by an immunocapture enzyme assay. The mean +/- SD concentration of CP detected by this assay in the NB4 cells, before any treatment, was 1.89 +/- 0.5 microgram/mg protein. Treatment of NB4 cells with 10(-6) M ATRA for 5 days significantly decreased the expression of CP, which became virtually undetectable by the clotting assay, and was 64% less than the untreated control by the immunocapture enzyme assay. This study provides the first evidence that the human promyelocytic cell line NB4 possess CP. The expression of this procoagulant is modulated by ATRA.
Leukemia 1994 Jan
PMID:Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation by all-trans-retinoic acid. 828 80

The plasma tissue factor (TF) antigen level was measured in patients with disseminated intravascular coagulation (DIC). The plasma TF antigen was detected in normal volunteers, and it was significantly higher in DIC patients than in non-DIC patients. However, in some patients with DIC, the plasma TF antigen level was within the normal range. The plasma TF antigen level in patients with DIC significantly decreased after therapy, but it was not correlated with organ failure or outcome. The plasma TF antigen level in patients with DIC was not correlated with other hemostatic markers. The plasma TF antigen level tended to be higher in DIC patients with nonlymphoid leukemia than in those with lymphoid tumor. TF might be implicated in the occurrence and progression of DIC.
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PMID:Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. 829 94

Disturbances in the regulation of the balance between the fibrinolytic and procoagulant properties of leukemic cells may contribute to the coagulopathy of acute leukemia. The coagulant response to a number of stimuli is regulated by the expression of tissue factor, but the role of the plasminogen activator inhibitors, PAI-1 and PAI-2, in contributing to the net coagulant response is not known. In this study, we have examined the production of these proteins by cultured myeloid leukemic cells arrested at different stages of differentiation. Northern blot analysis showed time-dependent and differential production of mRNA for PAI-2 and tissue factor, and to a much lesser extent, PAI-1, in response to the differentiating agent, 12-phorbol-13-myristate acetate. The capacity to synthesize PAI-2 appeared to be related to the stage of myeloid cell differentiation. Examination of the gene products by immunoblot analysis demonstrated multiple forms of PAI-2 in all myeloid cells examined. In addition, a common characteristic of all the myeloid cells was the production of a high molecular weight species of tissue factor which may be a secreted form unique to leukemic cells. Taken together, the findings demonstrate that myeloid leukemic cells are capable of generating a multicomponent coagulant response.
Leukemia 1993 Jun
PMID:Tissue factor and plasminogen activator inhibitor expression in the differentiation of myeloid leukemic cells. 830 77

Tissue factor (TF) exists in a cryptic form [i.e. without procoagulant activity (PCA)] in peripheral blood monocytes and quiescent tissue macrophages but is expressed constitutively in most human tumor cells. Induction and cell surface expression of TF in these cells in vivo is associated with activation of intravascular and extravascular coagulation in patients with a variety of inflammatory or malignant diseases. The regulation of TF synthesis in cells is complex and new information from transfection studies suggests that changes in cellular glycosylation pathways impair cell surface expression of functional TF. Such dysregulation may also characterize the lineage-unfaithful expression of TF in leukemic cells and perhaps explain some of the thrombohemorrhagic complications in patients with acute progranulocytic leukemia. The importance of carbohydrate modification of TF is reviewed.
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PMID:Tissue factor expression in human leukocytes and tumor cells. 857 92

In order to assess the clinical implication of tissue factor pathway inhibitor (TFPI) in disseminated intravascular coagulation (DIC), plasma concentrations of TFPI were measured together with plasma tissue factor (TF) in 30 healthy subjects and 49 patients with DIC associated with a variety of underlying diseases. The mean TFPI concentration was elevated in patients with DIC at presentation (205.8 +/- SD 79.1 ng/ml) as compared with healthy subjects (97.3 +/- 22.2 ng/ml, P < 0.001). The mean plasma TF concentration in patients with DIC (412.7 +/- 445.7 pg/ml) was also higher than that in healthy subjects (137.5 +/- 50.6 pg/ml, P < 0.001). Elevated TF levels were found predominantly in patients with DIC caused by cancer and leukemia, whereas TFPI was elevated in all underlying disease categories. Plasma TFPI concentration did not correlate with plasma TF. In addition, hemostatic markers of DIC such as thrombin-antithrombin complex, prothrombin fragment 1 + 2, plasmin-plasmin inhibitor complex, FDP or fibrinogen did not correlate with TFPI. Serial determinations of plasma TFPI in each patient demonstrated that the behavior of TFPI was independent of the changes in plasma TF and other hemostatic parameters. These findings indicate that plasma TFPI does not decrease in DIC and is not valuable for monitoring the progress of DIC.
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PMID:Plasma tissue factor pathway inhibitor in disseminated intravascular coagulation: comparison of its behavior with plasma tissue factor. 858 47


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