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PMID: 17574023 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency.

Cell ·Vol. 129 ·No. 6 ·2007-06-15 ·Pages 1097-110

Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, Westmoreland SV, Chambon P, Scadden DT, Purton LE

Abstract

Myeloproliferative syndromes (MPS) are a heterogeneous subclass of nonlymphoid hematopoietic neoplasms which are considered to be intrinsic to hematopoietic cells. The causes of MPS are largely unknown. Here, we demonstrate that mice deficient for retinoic acid receptor gamma (RARgamma), develop MPS induced solely by the RARgamma-deficient microenvironment. RARgamma(-/-) mice had significantly increased granulocyte/macrophage progenitors and granulocytes in bone marrow (BM), peripheral blood, and spleen. The MPS phenotype continued for the lifespan of the mice and was more pronounced in older mice. Unexpectedly, transplant studies revealed this disease was not intrinsic to the hematopoietic cells. BM from wild-type mice transplanted into mice with an RARgamma(-/-) microenvironment rapidly developed the MPS, which was partially caused by significantly elevated TNFalpha in RARgamma(-/-) mice. These data show that loss of RARgamma results in a nonhematopoietic cell-intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic disorders.

MeSH Terms
Animals Bone Marrow/metabolism Bone Marrow Cells/cytology Cell Transplantation Granulocytes/cytology Macrophages/cytology Mice Mice, Inbred C57BL Mice, Transgenic Models, Biological Myeloproliferative Disorders/genetics,metabolism Phenotype Receptors, Retinoic Acid/genetics,physiology Signal Transduction Stem Cells/cytology
Chemicals
Receptors, Retinoic Acid retinoic acid receptor gamma
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Walkley Carl R
Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia.
Olsen Gemma Haines
Dworkin Sebastian
Fabb Stewart A
Swann Jeremy
McArthur Grant A
Westmoreland Susan V
Chambon Pierre
Scadden David T
Purton Louise E
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.05.014
Published
2007-06-15
Pages
1097-110
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC1974882
Subset
IM
Grants
NIDDK NIH HHS · DK84551 · United States
NHLBI NIH HHS · R01 HL044851 · United States
NIDDK NIH HHS · R21 DK071773-02 · United States
NHLBI NIH HHS · R01 HL044851-14 · United States
NIDDK NIH HHS · R21 DK071773 · United States
NIDDK NIH HHS · DK71773 · United States
NIDDK NIH HHS · R21 DK071773-01A1 · United States
Corrections
CommentIn
PMID: 17574018
External Links
PubMed source DOI: 10.1016/j.cell.2007.05.014 PMC Full Text View journal details
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