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Recent News and Articles on the Keywords: research illuminates + acute promyelocytic + research  Related to the article below (Last Update: 5/5/2008)

British team discovers obesity gene
Times Online, UK -
The discovery also illuminates the importance of ?junk DNA? ? the 98 per cent of the genome that does not contain protein-making genes, and was once thought ...
LED lights shine at saving energy in tech gear
San Francisco Chronicle,  USA -
As Dash explained, behind the flat-panel display in a typical laptop there sits a thin fluorescent lightbulb that illuminates the back of the screen. ...
The rise and fall of Nim Chimpsky
PSU Daily Vanguard, OR - Apr 30, 2008
Hess tells the story of Nim's tribulations with much compassion, and also illuminates the power politics at play in Project Nim. ...
Constance Backhouse, Sherrill Grace, Frank Hawthorne, Peter St ...
Government of Canada Newsroom (press release), Canada - Apr 29, 2008
Backhouse illuminates key social justice themes of the 19 th and 20 th centuries. Her book The Secret Oppression: Sexual Harassment of Working Women (1979), ...
High Performing Sales Forces Follow Same Path to Excellence
PR Newswire (press release), NY - Apr 29, 2008
The research report illuminates the current state of affairs at best-in- class organizations, such as Pfizer, General Electric, Johnson & Johnson, Kraft, ...
Pulitzer Prize Winner Brooks Inspired by a True Story
Authorlink (subscription), TX - May 1, 2008
It seduces us into a sense of connection with people whose lives couldn?t be more different from our own yet illuminates our commonalities. ...
High-Throughput Sequencing Illuminates Arabidopsis Epigenome
GenomeWeb News (subscription), NY - Apr 18, 2008
By Andrea Anderson NEW YORK (GenomeWeb News) ? New research is providing a roadmap of the epigenetic DNA modifications that help orchestrate the gene ...
Columbia recognizes pathway between Alzheimer?s and stroke
iTWire, Australia - Apr 19, 2008
[Columbia University Medical Center: ?Research illuminates link between Alzheimer?s and stroke?] Duff?s Columbia laboratory is currently working on ...
Scholarship illuminates more corners of Holocaust's abiding mystery
Minneapolis Star Tribune, MN - Apr 27, 2008
In a few months, independent investigators plan to launch a Web site with their nearly 20-year research into Russian archives and prison records. ...
Scholarship illuminates more corners of Holocaust's abiding ...
Minneapolis Star Tribune, MN - Apr 28, 2008
Independent research suggests he may have lived many years ? perhaps to the late 1980s. If true, he likely was held in isolation, stripped of his identity, ...
Source: Google News

Interferon regulatory factor-1 myelodysplasia and leukemia -
DA Liebermann, B Hoffman - Leukemia Research, 2006 - Elsevier
... to induce clinical remission in patients with acute promyelocytic leukemia [22 ...
Undoubtedly fortcoming research will further illuminate molecular pathways ...

[PDF] Molecular genetics and structural genomics of the human protein kinase C gene module -
K Kofler, M Erdel, G Utermann, G Baier - Genome Biol, 2002 - biomedcentral.com
Page 1. http://genomebiology.com/2002/3/3/research/0014.1 comment reviews reports
deposited research interactions information refereed research ...

MINI REVIEW TUMOR REVERSION: CORRECTION OF MALIGNANT BEHAVIOR BY MICROENVIRONMENTAL CUES -
PA Kenny, MJ Bissell - Int. J. Cancer, 2003 - doi.wiley.com
... of Defense Breast Cancer Research Program; Grant ... of the initiating oncogene and
illuminate the signal ... ACUTE PROMYELOCYTIC LEUKEMIA: FROM BENCH TO BEDSIDE The ...

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9 -
Z Liu, J Shen, JM Carbrey, R Mukhopadhyay, P Agre, … - Proceedings of the National Academy of Sciences, 2002 - National Acad Sciences
... on reports by the US National Research Council (37 ... and levels of expression, could
illuminate reasons for ... for the treatment of acute promyelocytic leukemia (39 ...

Fluorescent cobalamins and uses thereof -
CB Grissom, FG West, J McGreevy, JS Bentz, MJ … - US Patent 6,797,521, 2004 - freepatentsonline.com
... Assignee: University of Utah Research Foundation (Salt Lake City ... materials used herein
to illuminate the background ... In acute promyelocytic leukemia, a 3-26 fold ...

P53 and PML: new partners in tumor suppression -
V Gottifredi, C Prives - Trends in Cell Biology, 2001 - Elsevier
... Research update. ... of a functional link between PML with both p53 and Rb can also
illuminate our understanding of acute promyelocytic leukemia. ...

Mortality in Overweight and Underweight Children With Acute Myeloid Leukemia -
BJ Lange, RB Gerbing, J Feusner, J Skolnik, N … - JAMA, 2005 - Am Med Assoc
... that underweight children with acute lymphoblastic leukemia and ... The study does not
illuminate the causes of ... Clinical research associates, supported fully or in ...

Nuclear bodies: multifaceted subdomains of the interchromatin space -
AG Matera - Trends in Cell Biology, 1999 - Elsevier
... subject of a great deal of research in recent ... 1). Most coiled bodies [(c), green]
and promyelocytic leukaemia (PML ... in panels (c) and (e) to illuminate the nuclei ...

Chromatin targets: reading and writing the cancer cell epigenome
FD Urnov - Drug Discovery Today: Disease Models, 2004 - Elsevier
... stand so as to move their research into the ... of an HDACi in patients with acute
promyelocytic leukemia (APL ... of purified enzyme and substrate illuminates none of ...
-

Designed transcription factors as structural, functional and therapeutic probes of chromatin in vivo … -
FD Urnov - EMBO Reports, 2002 - pubmedcentral.nih.gov
... effective in diseases such as acute promyelocytic leukemia (APL ... many authors of
important primary research studies whose ... did so much to illuminate the central ...

Source: Google Scholar

Research Illuminates Important Insights Into Acute Promyelocytic Leukemia
Results from two new studies provide key mechanistic insights into the complex molecular events that cause a deadly type of leukemia. The research, published in the July issue of the journal Cancer Cell, published by Cell Press, illuminates specific mechanisms involved in development of acute promyelocytic leukemia (APL) and identifies promising new avenues to develop treatments for some of its variant forms.

APL is a cancer of the bone marrow that occurs when certain developing white blood cells get stuck at a highly proliferative and immature stage. The abnormal cells accumulate and eventually crowd out the normal, healthy blood cells. Most cases of APL are caused by the expression of the PML/RARA (promyelocytic leukemia/retinoic acid receptor alpha) oncogene.
This oncogene is formed by an abnormal translocation between two chromosomes and gives rise to a protein called a fusion protein. In APL, the fusion protein, always involving the transcription factor RARA, acts as a potent transcriptional repressor that interferes with gene expression and prevents normal differentiation of white blood cells. Previous work of these two groups suggested that PML/RARA self-association, called homodimerization, and posttranslational modifications are important for transformation. In addition, retinoid X receptor (RXR) has been shown to be present in the DNA-bound PML/RARA oncogenic complex and is thought to play a role in the ability of the fusion protein to bind to DNA and regulate gene expression.

Dr. Chi Wai Eric So from The Institute of Cancer Research in London and Dr. Shuo Dong from Baylor College of Medicine in Houston and their colleagues characterized the transformation mechanisms involved in APL by functionally separating homodimerization and the intrinsic DNA-binding properties of RARA fusions from transformation of primary blood cells. The researchers found that homodimerization was not sufficient for RARA fusion-mediated transformation, but higher-order RXRA/RAR fusion hetero-oligomeric complexes that aberrantly recruit transcriptional corepressors to downstream targets were essential. Importantly, disruption of RXR-dependent pathways suppressed RARA fusion-mediated transformation. The authors also suggest that disruption of homotetramers into homodimers may be sufficient to abrogate the transformation ability of RARA fusion proteins. "These findings not only identify the key elements and potential avenues for therapeutic targeting of RARA-mediated leukemia but also shed light on oligomeric transformation mechanisms reported with various leukemia-associated transcription factors," conclude Drs. So and Dong.

A separate group, led by Dr. Hugues de Thé from CNRS/University of Paris 7, investigated the role of RXR in the PML/RARA complex through a variety of experiments that revealed that, although not required for transformation of blood cells in primary culture, RXR was absolutely essential for APL development in PML/RARA transgenic mice. Pharmacological activation of RXR relieved PML/RARA-induced transcriptional repression and triggered APL differentiation only when RXR was in a complex with PML/RARA. In addition, PML/RARA promoted posttranslational modifications of RXR, including its sumoylation, a modification that triggers transcriptional repression for RXR and many other transcription factors. "The presence of RXR in the PML/RARA complex not only greatly facilitates DNA binding but is also required for rexinoid-induced differentiation, demonstrating that RXR is not a silent partner but a critical determinant of transformation. In addition, our observations suggest that dysregulated sumoylation induced by PML/RARA may contribute to altered gene expression and APL pathogenesis," explains Dr. de Thé.
Taken together, results from these studies indicate that formation of higher-order homotetrameric complexes and recruitment of RXR are essential components of RARA-induced transformation and that RXR is a key member of the PML/RARA-associated oncogenic response that facilitates PML/RARA-induced transformation through multiple mechanisms and participates in the differentiation response. Further, homotetrameric complexes and RXR have the potential to be useful therapeutic targets for RARA fusion-mediated cancers.

The researchers include Jun Zhu of CNRS/University Paris in Paris Cedex and CNRS laboratoire international associé MPC, Shanghai Institute of Hematology, Rui Jin Hospital in Shanghai; Rihab Nasr, Laurent Pérès, Florence Riaucoux-Lormière, Nicole Honoré, Caroline Berthier, and Dmitrii Kamashev of CNRS/University Paris in Paris Cedex; Jun Zhou of CNRS/University Paris in Paris Cedex; Dominique Vitoux, Catherine Lavau, of CNRS/University Paris in Paris Cedex; Hugues de Thé of CNRS/University Paris in Paris Cedex. This work was supported by the INCa/Canceropole, ARECA, P2R, ATIP, National Natural Science Foundation of China (30525006), and EPITRON, an Integrated Project funded by the European Union under the 6th Framework Programme (LSHC-CT-2005-518417).

Zhu et al.: "RXR Is an Essential Component of the Oncogenic PML/RARA Complex In Vivo." Publishing in Cancer Cell 12, 23¨C35, July 2007 DOI 10.1016/j.ccr.2007.06.004 http://www.cancercell.org/.

The researchers include Bernd B. Zeisig, Colin Kwok, Arthur Zelent of The Institute of Cancer Research in Greater London; Pattabhiraman Shankaranarayanan and Hinrich Gronemeyer of Institut de Genetique et de Biologie Moleculaire et Cellulaire in Strasbourg; Shuo Dong of Baylor College of Medicine in Houston; Chi Wai Eric So of The Institute of Cancer Research in Greater London. This research is supported by project grants from Cancer Research UK (C.W.E.S.), the Leukaemia Research Fund (C.W.E.S.), European Union EPITRON LSHC-CT2005-518417 (H.G.), X-TRA-NET LSHG-CT2005-018882 (H.G.), and the Ligue Nationale contre le Cancer (H.G., équipe labelisée), and R21 grant CA119080 (S.D.) from the National Cancer Institute.

Zeisig et al.: "Recruitment of RXR by Homotetrameric RAR¦Á Fusion Proteins Is Essential for Transformation." Publishing in Cancer Cell 12, 36¨C51, July 2007 DOI 10.1016/j.ccr.2007.06.006 http://www.cancercell.org/.

Source: Erin Doonan
Cell Press
 
 
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