Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells

Objective To study the effect of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. Methods PGA from freshly isolated APL blasts from APL patients treated with ATRA or As2O3 was detected using a one-stage clotting assay. TF antigen was detected by ELISA and TF mRNA by RT-PGR. 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 As2O3, were also examined. Results Both ATRA and As2O3 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 As2O3 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 As2O3. By down-regulating TF expression, As2O3 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 As2O3 on TF expression in U937 cells might not involve this fusion protein.