| PML-RAR{alpha} and Dnmt3a1 cooperate in vivo to promote acute promyelocytic leukemia. | |
| | |
MedLine Citation:
|
PMID:Â 20861188 Â Â Â Owner:Â NLM Â Â Â Status:Â MEDLINE Â Â Â |
Abstract/OtherAbstract:
|
The PML-RARα oncogene is the central effector of acute promyelocytic leukemia (APL). PML-RARα physically interacts with epigenetic-modifying enzymes including DNA methyltransferases (Dnmt) to suppress critical downstream targets. Here, we show that increased expression of Dnmt3a1 cooperates with PML-RARα in vivo to promote early lethality secondary to myeloid expansion and dysfunction in primary mice. Bone marrow cells from these mice cause leukemogenesis with a shortened latency and a higher penetrance on transplantation into irradiated recipients. Furthermore, leukemic cells overexpressing PML-RARα and Dnmt3a1 display increased methylation at a target promoter compared with PML-RARα or Dnmt3a1 controls. Our findings show a cooperation between the PML-RARα oncogene and the Dnmt3a1 enzyme in vivo and that Dnmt levels can be rate limiting in APL progression. |
| | |
Authors:
|
Deepa Subramanyam; Cassandra D Belair; Keegan Q Barry-Holson; Haijiang Lin; Scott C Kogan; Emmanuelle Passegué; Robert Blelloch |
Related Documents
:
|
12808098Â -Â Cooperation of cytokine signaling with chimeric transcription factors in leukemogenesis... 12022398Â -Â Outbreak of hind limb paralysis in young cfw swiss webster mice. 20647568Â -Â A protease-resistant pml-rar{alpha} has increased leukemogenic potential in a murine mo... 23585228Â -Â Impairment of autophagy decreases ventilator-induced lung injury by blockade of the nfÎ... 9003248Â -Â Analysis of b7-1 and b7-2 costimulatory ligands in cultured mouse microglia: upregulati... 17089128Â -Â Blockade of stat3 by antisense oligonucleotide in tnbs-induced murine colitis. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    Date: 2010-09-21 |
Journal Detail:
|
Title: Cancer research    Volume: 70    ISSN: 1538-7445    ISO Abbreviation: Cancer Res.    Publication Date: 2010 Nov |
Date Detail:
|
Created Date:Â 2010-11-02 Â Â Â Completed Date:Â 2010-12-21 Â Â Â Revised Date:Â 2013-05-27 Â Â Â |
Medline Journal Info:
|
Nlm Unique ID: 2984705R    Medline TA: Cancer Res    Country: United States    |
Other Details:
|
Languages: eng    Pagination: 8792-801    Citation Subset: IM    |
Copyright Information:
|
©2010 AACR. |
Affiliation:
|
Institute for Regeneration Medicine, University of California, San Francisco, California 94143, USA. |
Export Citation:
|
APA/MLA Format    Download EndNote    Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bone Marrow Cells / pathology DNA (Cytosine-5-)-Methyltransferase / genetics* DNA Methylation* Flow Cytometry Genes, Lethal* Humans Inflammation / etiology, pathology Leukemia, Promyelocytic, Acute / etiology*, pathology Mice Mice, Transgenic Oncogene Proteins, Fusion / genetics* Promoter Regions, Genetic / genetics Respiratory Burst Survival Rate |
| Grant Support | |
ID/Acronym/Agency:
|
K08 NS048118-01A1/NS/NINDS NIH HHS; K08 NS048118-02/NS/NINDS NIH HHS; K08 NS048118-03/NS/NINDS NIH HHS; K08 NS048118-04/NS/NINDS NIH HHS; K08 NS048118-05/NS/NINDS NIH HHS; K08 NS048118-06/NS/NINDS NIH HHS; K08 NS48118/NS/NINDS NIH HHS; R01 CA095274/CA/NCI NIH HHS; R01 CA095274-09/CA/NCI NIH HHS; R01 NS057221-01A1/NS/NINDS NIH HHS; R01 NS057221-02/NS/NINDS NIH HHS; R01 NS057221-03/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Oncogene Proteins, Fusion; 0/promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA methyltransferase 3A |
| Comments/Corrections | |
Erratum In:
|
Cancer Res. 2011 Apr 1;71(7):2805 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell t...
Next Document: Tumor-reactive CD8+ early effector T cells identified at tumor site in primary and metastatic melano...