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

Shanghai Institute of Hematology, Ruijin Hospital Affiliated Shanghai Second Medical University, Shanghai 200025, China.

OBJECTIVE: To study the effect of all-trans retinoic acid (ATRA) and arsenic troxide (As2O3) 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 As2O3 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 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.

PMID: 11779431 [PubMed - indexed for MEDLINE]