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Recent News and Articles on the Keywords: into + insights + promyelocytic  Related to the article below (Last Update: 8/5/2008)

Leukemia Journal Publishes Results from Darinaparsin Study
MarketWatch -
"The successful application of a treatment that offers inorganic arsenic's efficacy in acute promyelocytic leukemia, to other more common malignancies, ...
Source: Google News

Myeloperoxidase biosynthesis by a human promyelocytic leukemia cell line: insight into … -
WM Nauseef - Blood, 1986 - ncbi.nlm.nih.gov
Click here to read Myeloperoxidase biosynthesis by a human promyelocytic leukemia
cell line: insight into myeloperoxidase deficiency. Nauseef WM. ...

New Insights into the Pathogenesis of Coagulation Dysfunction in Acute Promyelocytic Leukemia -
MS Tallman, D Hakimian, HC Kwaan, FR Rickles - Leukemia and Lymphoma, 1993 - informaworld.com
... States of America New Insights into the Pathogenesis of Coagulation Dysfunction
in Acute - Promyelocytic Leukemia MARTIN S. TALLMAN ...

New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate … -
MA Sirover - Biochimica et Biophysica Acta (BBA)/Protein Structure and …, 1999 - Elsevier
... To gain insight into mechanisms of endocytosis, CHO ... tubulin polymerization (ie, bundling)
into microtubules is an ... binding of the promyelocytic leukemia protein ...

New insights into the pharmacodynamic and pharmacokinetic properties of statins -
A Corsini, S Bellosta, R Baetta, R Fumagalli, R … - Pharmacology and Therapeutics, 1999 - Elsevier
... Inc. All rights reserved. Review article. New insights into the pharmacodynamic
and pharmacokinetic properties of statins. Alberto ...

Insights into myeloperoxidase biosynthesis from its inherited deficiency -
WM Nauseef - Journal of Molecular Medicine, 1998 - Springer
... Nauseef WM (1986) Myeloperoxidase biosynthesis by a human promyelocytic leukemia
cell line: insight into myeloperoxidase deficiency. Blood 67:865 64. ...

Syndrome of resistance to thyroid hormone: insights into thyroid hormone action -
P Kopp - Experimental Biology and Medicine, 1996 - SEBM
... and their mutated receptors has provided important insights into the mechanisms ...
PML-RARalpha after multiple relapses of acute promyelocytic leukemia: analysis ...

[CITATION] New insights into the role of nuclear factor-B, a ubiquitous transcription factor in the initiation …
F Chen, V Castranova, X Shi, LM Demers - Clin Chem, 1999

Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9) -
C Kerkhoff, M Klempt, C Sorg - BBA-Molecular Cell Research, 1998 - Elsevier
... to specific stages of myeloid differentiation, the human promyelocytic leukemia
cell ... binding sites for the MRPs will provide new insights into the molecular ...

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients … -
TD Shanafelt, SM Geyer, NE Kay - Blood, 2004 - bloodjournal.hematologylibrary.org
... REVIEW ARTICLES. Prognosis at diagnosis: integrating molecular biologic
insights into clinical practice for patients with CLL. Tait ...

Acute promyelocytic leukemia. New insights into diagnosis and therapy. -
SR Frankel - Hematol Oncol Clin North Am, 1993 - ncbi.nlm.nih.gov
Hematol Oncol Clin North Am. 1993 Feb;7(1):109-38. Acute promyelocytic leukemia.
New insights into diagnosis and therapy. Frankel SR. ...

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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