study the effect of all trans retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro Metho...study the effect of all trans retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro Methods PCA from freshly isolated APL blasts from APL patients treated with ATRA or As 2O 3 was detected using a one stage clotting assay TF antigen was detected by ELISA and TF mRNA by RT PCR The maturation sensitive (NB4) or resistant subclones (NB4 R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV PML RARa treated with or without ATRA or As 2O 3, were also examined Results Both ATRA and As 2O 3 can down regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time dependent manner The TF antigen level in PML RARa+ U937 cells was significantly higher than that in U937 cells infected with retrovirus vector Both ATRA and As 2O 3 can also down regulate the TF antigen in U937 cells transfected with or without PML RARa Conclusion Tissue factor expression and PCA in APL cells may be down regulated by ATRA and As 2O 3 By down regulating TF expression, As 2O 3 might also be used to improve the DIC related hemorrhage in APL Our data indicate that elevated TF antigen in PML RARa+ U937 may be related to the fusion protein PML RARa The down regulating effect of ATRA and As 2O 3 on TF expression in U937 cells might not involve this fusion展开更多
Objective To study in vivo effect of all trans retinoic acid (ATRA) or arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone...Objective To study in vivo effect of all trans retinoic acid (ATRA) or arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients Methods The plasma variables were measured by ELISA or chromogenic study The TF transcription was assessed using reverse transcription polymerase chain reaction technique (RT PCR) Results The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy The plasma level of platelet α granular membrane protein 140, soluble fibrinomonomer complex, thrombomo^dulin, tissue plasminogen activator and D dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, α2 plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group Conclusions There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment Both ATRA and As 2O 3 therapy down regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment展开更多
文摘study the effect of all trans retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro Methods PCA from freshly isolated APL blasts from APL patients treated with ATRA or As 2O 3 was detected using a one stage clotting assay TF antigen was detected by ELISA and TF mRNA by RT PCR The maturation sensitive (NB4) or resistant subclones (NB4 R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV PML RARa treated with or without ATRA or As 2O 3, were also examined Results Both ATRA and As 2O 3 can down regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time dependent manner The TF antigen level in PML RARa+ U937 cells was significantly higher than that in U937 cells infected with retrovirus vector Both ATRA and As 2O 3 can also down regulate the TF antigen in U937 cells transfected with or without PML RARa Conclusion Tissue factor expression and PCA in APL cells may be down regulated by ATRA and As 2O 3 By down regulating TF expression, As 2O 3 might also be used to improve the DIC related hemorrhage in APL Our data indicate that elevated TF antigen in PML RARa+ U937 may be related to the fusion protein PML RARa The down regulating effect of ATRA and As 2O 3 on TF expression in U937 cells might not involve this fusion
文摘Objective To study in vivo effect of all trans retinoic acid (ATRA) or arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients Methods The plasma variables were measured by ELISA or chromogenic study The TF transcription was assessed using reverse transcription polymerase chain reaction technique (RT PCR) Results The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy The plasma level of platelet α granular membrane protein 140, soluble fibrinomonomer complex, thrombomo^dulin, tissue plasminogen activator and D dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, α2 plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group Conclusions There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment Both ATRA and As 2O 3 therapy down regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment
