|
|
 Previous Article | Table of Contents | Next Article 
Anticoagulant effects of retinoic acids on leukemia cells
T Saito, T Koyama, K Nagata, R Kamiyama and S Hirosawa
School of Allied Health Sciences, Tokyo Medical and Dental University,
Japan.
We have recently found that all-trans retinoic acid (ATRA) upregulates
thrombomodulin (TM) and downregulates tissue factor (TF) expression in
acute myelogenous leukemia (AML) M3 cells (NB4) and acute monoblastic
leukemia cells (U937) (Koyama et al, Blood 84:3001, 1994). We have further
investigated the effects of ATRA on leukemic cells freshly isolated from
patients at diagnosis. Increase of TM antigen was documented in all AML
cells: M0 (n = 1), M2 (n = 5), M3 (n = 3), M4 (n = 3), M5 (n = 3), and M6
(n = 1). Decrease of TF antigen was observed in 4 M2, 1 M4, and all M3 and
M5 patients. However, no TM and TF antigens were detected in all chronic
lymphocytic leukemia cells (n = 3) with or without ATRA treatment. Changes
of TM and TF antigen levels were associated with those of TM and TF
cofactor levels on the cell surface. A stereoisomer of RA, 9-cis RA, is a
high-affinity ligand for the RA receptors (RARs) and the retinoid X
receptors, although ATRA and another isomer, 13-cis RA, solely bind to
RARs. We have also studied the effects of 9-cis RA and 13-cis RA on the
expressions of TM and TF in NB4 and U937 cells. A relatively wide range of
9-cis RA concentrations (0.01 to 1 mumol/L) compared with ATRA was optimal
for prolongation of normal plasma-based recalcification time (reduction of
cell surface TF activity), decrease of TF antigen, and increase of TM
antigen on the surface and in the lysates of NB4 and U937 cells. Western
blot analysis under nonreducing conditions showed that both ATRA and 9-cis
RA markedly induced the prominent band at 75 kD of TM and reduced the band
at 45 kD of TF. Northern blot analysis has shown similar changes of mRNA
levels, which indicates that RAs regulate TM and TF expression in leukemic
cells at transcriptional levels. Anticoagulant effects of ATRA, ie,
upregulation of TM expression and downregulation of TF expression, are
applied not only to established cell lines of specific subtypes (M3 and M5)
but also to more universal AML (most cases of M3 and M5 and a part of the
other types of AML) cells freshly isolated from patients. 9-cis RA may be
more effective than ATRA as an inducer of differentiation of AML M3 cells
and as an anticoagulant agent for patients with certain types of AML as
well.
Volume 87,
Issue 2,
pp. 657-665,
01/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. M. Kuderer, T. L. Ortel, and C. W. Francis
Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival
J. Clin. Oncol.,
October 10, 2009;
27(29):
4902 - 4911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T.-P. Poon, C. P.-Y. Lau, J. W.-Y. Ho, W.-C. Yu, S.-T. Fan, and J. Wong
Tissue Factor Expression Correlates with Tumor Angiogenesis and Invasiveness in Human Hepatocellular Carcinoma
Clin. Cancer Res.,
November 1, 2003;
9(14):
5339 - 5345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ohsawa, T. Koyama, K. Yamamoto, S. Hirosawa, S. Kamei, and R. Kamiyama
1{alpha},25-Dihydroxyvitamin D3 and Its Potent Synthetic Analogs Downregulate Tissue Factor and Upregulate Thrombomodulin Expression in Monocytic Cells, Counteracting the Effects of Tumor Necrosis Factor and Oxidized LDL
Circulation,
December 5, 2000;
102(23):
2867 - 2872.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.-X. Cheng, X.-H. Zhu, X.-Q. Men, L. Wang, Q.-H. Huang, X. L. Jin, S.-M. Xiong, J. Zhu, W.-M. Guo, J.-Q. Chen, et al.
Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha
PNAS,
May 25, 1999;
96(11):
6318 - 6323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Falanga, R. Consonni, M. Marchetti, G. Locatelli, E. Garattini, C. G. Passerini, S.G. Gordon, and T. Barbui
Cancer Procoagulant and Tissue Factor Are Differently Modulated by All-trans-Retinoic Acid in Acute Promyelocytic Leukemia Cells
Blood,
July 1, 1998;
92(1):
143 - 151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Koyama, M. Shibakura, M. Ohsawa, R. Kamiyama, and S. Hirosawa
Anticoagulant Effects of 1alpha ,25-Dihydroxyvitamin D3 on Human Myelogenous Leukemia Cells and Monocytes
Blood,
July 1, 1998;
92(1):
160 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Barbui, G. Finazzi, and A. Falanga
The Impact of All-trans-Retinoic Acid on the Coagulopathy of Acute Promyelocytic Leukemia
Blood,
May 1, 1998;
91(9):
3093 - 3102.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shibakura, T. Koyama, T. Saito, K. Shudo, N. Miyasaka, R. Kamiyama, and S. Hirosawa
Anticoagulant Effects of Synthetic Retinoids Mediated Via Different Receptors on Human Leukemia and Umbilical Vein Endothelial Cells
Blood,
August 15, 1997;
90(4):
1545 - 1551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
