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All-trans retinoic acid upregulates thrombomodulin and downregulates
tissue-factor expression in acute promyelocytic leukemia cells: distinct
expression of thrombomodulin and tissue factor in human leukemic cells
T Koyama, S Hirosawa, N Kawamata, S Tohda and N Aoki
First Department of Internal Medicine, Tokyo Medical and Dental University,
Japan.
The expressions of thrombomodulin (TM) and tissue factor (TF) by all- trans
retinoic acid (ATRA) were studied in human leukemic cell lines including
NB4 (acute promyelocytic leukemia) and U937 (monoblastic leukemia). ATRA
remarkably upregulated TM antigen expression in cell lysates as well as TM
cofactor activity on the cell surfaces of NB4. The level of TM mRNA in NB4
cells was increased by ATRA. Inherently procoagulant NB4 cells contained
markedly higher content of TF, which was efficiently reduced by ATRA.
Modest increase of TM and decrease of TF were observed when NB4 cells were
treated with dibutyryl cyclic adenosine monophosphate (dbcAMP). On the
other hand, both ATRA and dbcAMP showed dramatic increase of TM antigen
level and modest decrease of TF antigen in U937 cells. These results
suggest that ATRA regulates expressions of TM and TF antigens and activity
in NB4 and U937 cell lines, and provide evidence for a potential efficiency
of ATRA as a preventive and therapeutic agent for disseminated
intravascular coagulation in promyelocytic and monocytic leukemia.
Volume 84,
Issue 9,
pp. 3001-3009,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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