ALL-TRANS-RETINOIC ACID UP-REGULATES THROMBOMODULIN AND DOWN-REGULATES TISSUE-FACTOR EXPRESSION IN ACUTE PROMYELOCYTIC LEUKEMIA-CELLS - DISTINCT EXPRESSION OF THROMBOMODULIN AND TISSUE FACTOR IN HUMAN LEUKEMIC-CELLS

The expressions of thrombomodulin (TM) and tissue factor (TF) by all-t rans retinoic acid (ATRA) were studied in human leukemic cell lines in cluding NB4 (acute promyelocytic leukemia) and U937 (monoblastic leuke mia). ATRA remarkably upregulated TM antigen expression in cell lysate s as well as TM cofactor activity on the cell surfaces of NB4. The lev el of TM mRNA in NB4 cells was increased by ATRA. Inherently procoagul ant NB4 cells contained markedly higher content of TF, which was effic iently reduced by ATRA. Modest increase of TM and decrease of TF were observed when NB4 cells were treated with dibutyryl cyclic adenosine m onophosphate (dbcAMP). On the other hand, both ATRA and dbcAMP showed dramatic increase of TM antigen level and modest decrease of TF antige n in U937 cells. These results suggest that ATRA regulates expressions of TM and TF antigens and activity in NB4 and U937 cell lines, and pr ovide evidence for a potential efficiency of ATRA as a preventive and therapeutic agent for disseminated intravascular coagulation in promye locytic and monocytic leukemia. (C) 1994 by The American Society of He matology.