Document Detail


Rational targeting in acute promyelocytic leukemia.
MedLine Citation:
PMID:  20133971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute promyelocytic leukemia (ARL) is characterized by the nearly homogeneous expression of the fusion oncogenic protein PML-RARalpha and the testis-specific cyclin A1 protein, which are implicated in its pathogenesis. PML-RARalpha binds all-trans retinoic acid with high affinity inducing granulocytic differentiation and remission. Current approaches with high doses of single or combined all-trans retinoic acid and chemotherapeutic agents, though relatively efficacious in the beginning, are highly toxic with severe side-effects (retinoic acid syndrome) and are followed by relapse in a high proportion of patients. Here it is proposed that targeting APL with low levels of all-trans retinoic acid combined with small molecule inhibitors of cyclin-dependent kinases may have the potential to be equally or more efficacious as any of the current single or combined agent approaches, affording reduced toxicity and relapse rates.
Authors:
Nikolaos A Papanikolaou
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  In vivo (Athens, Greece)     Volume:  24     ISSN:  0258-851X     ISO Abbreviation:  In Vivo     Publication Date:    2010 Jan-Feb
Date Detail:
Created Date:  2010-02-05     Completed Date:  2010-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806809     Medline TA:  In Vivo     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  21-7     Citation Subset:  IM    
Affiliation:
Aristotle University of Thessaloniki, School of Medicine, Laboratory of Biological Chemistry, University Campus PO Box 1686, Thessaloniki 54124, Greece. papanikn@med.auth.gr
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / adverse effects,  therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / pharmacology,  therapeutic use
Cyclin-Dependent Kinases / antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Delivery Systems*
Drug Resistance, Neoplasm / drug effects
Enzyme Inhibitors / pharmacology
Humans
Leukemia, Promyelocytic, Acute / drug therapy*
Tretinoin / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 302-79-4/Tretinoin; EC 2.7.11.22/Cyclin-Dependent Kinases

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