W Guo1, H Wang, W Zhao. 1. Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Abstract
OBJECTIVE: To investigate the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on both tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: The PCA of APL blasts freshly isolated from the APL patients treated with ATRA or As(2)O(3) was detected using a one-stage clotting assay; the TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitivity (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line as well as U937 cells transfected with pMSCV-PML-RARa treated with or without ATRA or As(2)O(3) were also examined. RESULTS: Both ATRA and As(2)O(3) time-dependently down-regulated the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro. The TF antigen level in PML-RARa(+) U937 cells was significantly higher than that in U937 cells transfected with retrovirus vector (890 pg/8 x 10(5) +/- 80 pg/8 x 10(5) cell and 728 pg/8 x 10(5) +/- 86 pg/8 x 10(5) cell, respectively). Both ATRA and As(2)O(3) down-regulated the TF antigen of the U937 cells transfected with or without PML-RARa. CONCLUSION: Tissue factor expression and PCA of APL cells can be down-regulated by ATRA and As(2)O(3). By down-regulating the TF expression, As(2)O(3) might also be used to improve the DIC-related hemorrhage of APL. It is also suggested that elevated TF antigen in the PML-RARa(+) U937 cells may be related with the fusion protein PML-RARa, while the down-regulation effect of ATRA and As(2)O(3) on the TF expression of U937 cells might not be involved in the fusion protein.
OBJECTIVE: To investigate the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on both tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: The PCA of APL blasts freshly isolated from the APL patients treated with ATRA or As(2)O(3) was detected using a one-stage clotting assay; the TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitivity (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line as well as U937 cells transfected with pMSCV-PML-RARa treated with or without ATRA or As(2)O(3) were also examined. RESULTS: Both ATRA and As(2)O(3) time-dependently down-regulated the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro. The TF antigen level in PML-RARa(+) U937 cells was significantly higher than that in U937 cells transfected with retrovirus vector (890 pg/8 x 10(5) +/- 80 pg/8 x 10(5) cell and 728 pg/8 x 10(5) +/- 86 pg/8 x 10(5) cell, respectively). Both ATRA and As(2)O(3) down-regulated the TF antigen of the U937 cells transfected with or without PML-RARa. CONCLUSION:Tissue factor expression and PCA of APL cells can be down-regulated by ATRA and As(2)O(3). By down-regulating the TF expression, As(2)O(3) might also be used to improve the DIC-related hemorrhage of APL. It is also suggested that elevated TF antigen in the PML-RARa(+) U937 cells may be related with the fusion protein PML-RARa, while the down-regulation effect of ATRA and As(2)O(3) on the TF expression of U937 cells might not be involved in the fusion protein.