[Effects of all-trans retinoic acid and arsenic trioxide on tissue factor expression of acute promyelocytic leukemia cells].
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.


CONCLUSIONS
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.
Guo
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Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
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Zhao
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D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000970:Antineoplastic Agents; D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; D012333:RNA, Messenger; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D013925:Thromboplastin; D000077237:Arsenic Trioxide