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PPARΓ AGONISTS INHIBIT ADHESION SIGNAL TO ENDOTHELIAL CELLS IN THE DIFFERENTIATION INDUCTION OF HL-60 ACUTE PROMYELOCYTIC LEUKEMIA CELLS.
Author(s):
Jinny Park
,
Jinny Park
Affiliations:
Division of Hematology/Oncology, Department of Internal Medicine,Gachon University Gil Hospital,Incheon,Korea, Republic Of
Eun-Mi Noh
,
Eun-Mi Noh
Affiliations:
Biochemistry,Institute for Medical Sciences, Chonbuk National University Medical School,Jeonju,Korea, Republic Of
Ji-Won Yoon
,
Ji-Won Yoon
Affiliations:
Psychology,Fullerton College,Fullerton,United States
On-Yoo Hong
,
On-Yoo Hong
Affiliations:
Biochemistry,Institute for Medical Sciences, Chonbuk National University Medical School,Jeonju,Korea, Republic Of
Jong-Suk Kim
Jong-Suk Kim
Affiliations:
Biochemistry,Institute for Medical Sciences, Chonbuk National University Medical School,Jeonju,Korea, Republic Of
(Abstract release date: 05/18/17) EHA Library. Park J. 05/18/17; 182386; PB1672
Prof. Dr. Jinny Park
Prof. Dr. Jinny Park
Contributions
PDF Abstract
Abstract

Abstract: PB1672

Type: Publication Only

Background

All-trans retinoic acid (ATRA) has successfully been used in the treatment of acute promyelocytic leukemia (APL) patients, with a remission rate of greater than 90% .
Despite the high cure rates, induction mortality is a still a problem in APL. One of the most common causes of death was the differentiation syndrome (DS) . The early administration of high-dose dexamethasone at the onset of the first signs or symptoms of DS is crucial, however specific biological therapies to counteract the syndrome are still not available.
Peroxisome proliferator activated receptor gamma (PPARγ) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily, which is expressed in normal monocytes, various leukemias, and epithelial malignancies. PPARγ is highly induced in differentiating myeloid cells and subsequently contributes to their differentiation.
Differentiation induction of APL cells is associated with increased expression of specific adhesion molecules and inflammatory cytokines, which may promote activation, migration, and adhesion of these cells.

Aims
Here, we studied the effect of PPARγ agonists on the adhesion of a human leukemia cell line (HL-60) to endothelial cells.

Methods
Differentiation was determined by an increase in reactivity with the CD11b antibody. For the adhesion assay, the Matrigel transwell system was used.

Results
HL-60 cells were differentiated into macrophage-like cells by a PKC activator, 12-O-Tetradecanoylphorbol-13-acetate (TPA). During the differentiation of HL-60 cells, PPARγ agonists acitvate TPA-induced CD11b expression. However, PPARγ agonists completely blocked TPA-induced ICAM-1 expression of endothelial cells, which resulted in the inhibition of adhesion of HL-60 cells to endothelial cells. These responses also were reversed by PPARγ antagonist (GW9662), indicating that PPARγ agonists inhibits the adhesion of the HL-60 cells to endothelial cells through a PPARγ dependent mechanism.

Conclusion
These results suggest that PPARγ agonists inhibit TPA-induced adhesion signal in the between HL-60 cells and endothelial cells, and may control differentiation syndrome in APL patients.

Session topic: 3. Acute myeloid leukemia - Biology

Keyword(s): Endothelial cell, Differentiation, Acute Promyelocytic Leukemia

Abstract: PB1672

Type: Publication Only

Background

All-trans retinoic acid (ATRA) has successfully been used in the treatment of acute promyelocytic leukemia (APL) patients, with a remission rate of greater than 90% .
Despite the high cure rates, induction mortality is a still a problem in APL. One of the most common causes of death was the differentiation syndrome (DS) . The early administration of high-dose dexamethasone at the onset of the first signs or symptoms of DS is crucial, however specific biological therapies to counteract the syndrome are still not available.
Peroxisome proliferator activated receptor gamma (PPARγ) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily, which is expressed in normal monocytes, various leukemias, and epithelial malignancies. PPARγ is highly induced in differentiating myeloid cells and subsequently contributes to their differentiation.
Differentiation induction of APL cells is associated with increased expression of specific adhesion molecules and inflammatory cytokines, which may promote activation, migration, and adhesion of these cells.

Aims
Here, we studied the effect of PPARγ agonists on the adhesion of a human leukemia cell line (HL-60) to endothelial cells.

Methods
Differentiation was determined by an increase in reactivity with the CD11b antibody. For the adhesion assay, the Matrigel transwell system was used.

Results
HL-60 cells were differentiated into macrophage-like cells by a PKC activator, 12-O-Tetradecanoylphorbol-13-acetate (TPA). During the differentiation of HL-60 cells, PPARγ agonists acitvate TPA-induced CD11b expression. However, PPARγ agonists completely blocked TPA-induced ICAM-1 expression of endothelial cells, which resulted in the inhibition of adhesion of HL-60 cells to endothelial cells. These responses also were reversed by PPARγ antagonist (GW9662), indicating that PPARγ agonists inhibits the adhesion of the HL-60 cells to endothelial cells through a PPARγ dependent mechanism.

Conclusion
These results suggest that PPARγ agonists inhibit TPA-induced adhesion signal in the between HL-60 cells and endothelial cells, and may control differentiation syndrome in APL patients.

Session topic: 3. Acute myeloid leukemia - Biology

Keyword(s): Endothelial cell, Differentiation, Acute Promyelocytic Leukemia

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