scholarly journals Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice

1998 ◽  
Vol 78 (7) ◽  
pp. 878-884 ◽  
Author(s):  
Y Fukuchi ◽  
M Kizaki ◽  
K Kinjo ◽  
N Awaya ◽  
A Muto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukaemia ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Promyelocytic Leukaemia ◽  
Combined Immunodeficiency ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The cytokines IL-3 and GM-CSF regulate the transcriptional activity of retinoic acid receptors in different in vitro models of myeloid differentiation

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 746-753 ◽  
Author(s):  
Barton S. Johnson ◽  
LeMoyne Mueller ◽  
Jutong Si ◽  
Steven J. Collins
Keyword(s):  
Retinoic Acid ◽  
Transcriptional Activity ◽  
In Vitro Models ◽  
Myeloid Differentiation ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The disruption of retinoic acid receptor (RAR) activity that characterizes human acute promyelocytic leukemia (APL) is associated with a block to granulocytic differentiation indicating that RARs are critical regulators of normal myeloid differentiation. Nevertheless, how RAR activity might be regulated in the presumably homogenous concentration of retinoids in blood and bone marrow and how these receptors might interact with specific hematopoietic cytokines to regulate normal myeloid differentiation remain unclear. Here, using several cytokine-dependent in vitro models of myeloid development, it was observed that specific hematopoietic cytokines that normally regulate myeloid lineage commitment and differentiation (interleukin-3 and granulocyte-macrophage colony-stimulating factor) trigger the enhancement of both ligand-dependent and ligand-independent transcriptional activity of both endogenous and exogenous (transiently transfected) RARs. This cytokine-mediated enhancement of RAR activity is not associated with any observed changes in expression of the RARs or their respective coactivators/corepressors. These studies define a previously unknown cytokine-RAR interaction during myelopoiesis and suggest that RAR activation might be a critical downstream event following interleukin-3 and granulocyte-macrophage colony-stimulating factor signaling during myeloid differentiation. This observation of ligand-independent activation of RARs that is mediated by certain cytokines represents a new paradigm with respect to how RAR activity might be modulated during hematopoiesis and also suggests a molecular basis for the differential sensitivity of human acute myelogenous leukemia cells to retinoids.

scholarly journals Retinoids (all-trans and 9-cis retinoic acid) stimulate production of macrophage colony-stimulating factor and granulocyte-macrophage colony- stimulating factor by human bone marrow stromal cells

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4107-4115 ◽  
Author(s):  
H Nakajima ◽  
M Kizaki ◽  
A Sonoda ◽  
S Mori ◽  
K Harigaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Retinoic acids (RAs) exert pleiotropic effects on cellular growth and differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell lines and cells from patients with acute myelogenous leukemia (AML) in vitro. Despite information on the effects of RAs on hematopoietic cells, little is known about how RAs act on the hematopoietic microenvironment, especially on bone marrow stromal cells. Based on recent observations that various cytokines produced mainly by bone marrow stromal cells regulate hematopoiesis, we analyzed the effects of RAs on cytokine production by these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell line KM101, which produces macrophage colony-stimulating factor (M-CSF) and granulocyte- macrophage colony-stimulating factor (GM-CSF) constitutively, enhanced mRNA levels of both cytokines in a dose-dependent manner. Both RAs also stimulated M-CSF production from primary cultures of human bone marrow stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-alpha mRNA expression in a dose-dependent manner, but did not affect levels of RAR-alpha mRNA. These findings may have important biologic implications for both the role of RAs in hematopoiesis and the therapeutic effects of ATRA on the hematopoietic microenvironment in patients with acute promyelocytic leukemia (APL).

Establishment of human granulocyte-macrophage colony stimulating factor producing transgenic SCID mice

1996 ◽  
Vol 95 (3) ◽  
pp. 437-442 ◽  
Author(s):  
Yoshitaka Miyakawa ◽  
Yumi Fukuchi ◽  
Mamoru Ito ◽  
Kimio Kobayashi ◽  
Takashi Kuramochi ◽  
...  
Keyword(s):  
Scid Mice ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor
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