|
|
 Previous Article | Table of Contents | Next Article 
Novel retinoic acid, 9-cis retinoic acid, in combination with all-trans
retinoic acid is an effective inducer of differentiation of retinoic
acid-resistant HL-60 cells
M Kizaki, H Nakajima, S Mori, T Koike, M Morikawa, M Ohta, M Saito, HP Koeffler and Y Ikeda
Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
Recent studies have shown that a high proportion of patients with acute
promyelocytic leukemia (APL) achieve complete remission after treatment
with all-trans retinoic acid (RA). Nevertheless, despite an initial good
response, most patients that received continuous treatment with all-trans
RA relapse and develop RA-resistant disease. The 9-cis RA is a
high-affinity ligand for retinoid X receptors (RXRs) and also binds
efficiently to retinoic acid receptors (RARs); all-trans RA is a ligand for
RARs. Both alone are able to induce differentiation of wild-type HL- 60
cells. We found that neither all-trans RA nor 9-cis RA (< 2 x 10(-6)
mol/L) induced differentiation of RA-resistant HL-60 cells into either
mature granulocytes or monocytes. However, morphologic differentiation of
the RA-resistant HL-60 cells was induced by 10(-6) mol/L all-trans RA
combined with various concentrations (10(-12) to 10(-6) mol/L) of 9- cis
RA. Electron microscopic examination also confirmed that the combination of
both retinoids induced RA-resistant HL-60 cells to differentiate to mature
granulocytes. Functional analysis of differentiation (NBT reduction
activity) confirmed the necessity of both analogs to induce
differentiation. Also, expression of myeloid- specific differentiation
antigens (CD11b and CD14) as well as migration inhibitory factor-related
protein (MRP)-8/14 mRNAs were upregulated only in the presence of both
retinoids in a dose-dependent manner. In these conditions 3H-thymidine
incorporation was inhibited and numbers of viable cells were decreased,
suggesting that all-trans RA with 9-cis RA may inhibit cell growth and
induce differentiation of RA-resistant HL-60 cells into mature
granulocytes. These studies suggest that 9-cis RA in combination with
all-trans RA is an effective inducer of RA- resistant HL-60 cells and may
have implications for both the biology of retinoids and clinical treatment
of RA-resistant acute myelogenous leukemia, including APL patients.
Volume 83,
Issue 11,
pp. 3289-3297,
06/01/1994
Copyright © 1994 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:
|
|
|
|
 
T. Ikezoe, E. S. Daar, J.-i. Hisatake, H. Taguchi, and H. P. Koeffler
HIV-1 protease inhibitors decrease proliferation and induce differentiation of human myelocytic leukemia cells
Blood,
November 15, 2000;
96(10):
3553 - 3559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Wu, H.-T. Kim, J. L. Rodriquez, D. Munoz-Medellin, S. K. Mohsin, S. G. Hilsenbeck, W. W. Lamph, M. M. Gottardis, M. A. Shirley, J. G. Kuhn, et al.
9-cis-Retinoic Acid Suppresses Mammary Tumorigenesis in C3(1)-Simian Virus 40 T Antigen-transgenic Mice
Clin. Cancer Res.,
September 1, 2000;
6(9):
3696 - 3704.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Melnick and J. D. Licht
Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia
Blood,
May 15, 1999;
93(10):
3167 - 3215.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shiohara, M. I. Dawson, P. D. Hobbs, N. Sawai, T. Higuchi, K. Koike, A. Komiyama, and H. P. Koeffler
Effects of Novel RAR- and RXR-Selective Retinoids on Myeloid Leukemic Proliferation and Differentiation In Vitro
Blood,
March 15, 1999;
93(6):
2057 - 2066.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Matsushita, M. Kizaki, H. Kobayashi, H. Ueno, A. Muto, N. Takayama, N. Awaya, K. Kinjo, Y. Hattori, and Y. Ikeda
Restoration of Retinoid Sensitivity by MDR1 Ribozymes in Retinoic Acid-Resistant Myeloid Leukemic Cells
Blood,
April 1, 1998;
91(7):
2452 - 2458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
