Document Detail


Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing.
MedLine Citation:
PMID:  21109770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Translocation (12;21), the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia, creates TEL/AML1 fusion gene. Resulting hybrid protein was shown to have a role in pre-leukemia establishment. To address its role for leukemic cell survival, we applied RNA interference to silence TEL/AML1 in leukemic cells. We designed and tested 11 different oligonucleotides targeting the TEL/AML1 fusion site. Using most efficient siRNAs, we achieved an average of 74-86% TEL/AML1 protein knockdown in REH and UOC-B6 leukemic cells, respectively. TEL/AML1 silencing neither decreased cell viability, nor induced apoptosis. On the contrary, it resulted in the modest but significant increase in the S phase fraction and in higher proliferation rate. Opposite effects on cell cycle distribution and proliferation were induced by AML1 silencing, thus, supporting our hypothesis that TEL/AML1 may block AML1-mediated promotion of G1/S progression through the cell cycle. In line with the lack of major effect on phenotype, we found no significant changes in clonogenic potential and global gene expression pattern upon TEL/AML1 depletion. Our data suggest that though TEL/AML1 is important for the (pre)leukemic clone development, it may be dispensable for leukemic cell survival and would not be a suitable target for gene-specific therapy.
Authors:
M Zaliova; J Madzo; G Cario; J Trka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-26
Journal Detail:
Title:  Leukemia     Volume:  25     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-09     Completed Date:  2011-04-08     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  313-20     Citation Subset:  IM    
Affiliation:
CLIP, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic. marketa.zaliova@lfmotol.cuni.cz
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle
Cell Line, Tumor
Cell Survival*
Clone Cells
Core Binding Factor Alpha 2 Subunit / genetics,  physiology*
Humans
Leukemia / pathology*
Oncogene Proteins, Fusion / genetics,  physiology*
RNA Interference*
RNA, Small Interfering / pharmacology*
Chemical
Reg. No./Substance:
0/Core Binding Factor Alpha 2 Subunit; 0/Oncogene Proteins, Fusion; 0/RNA, Small Interfering; 0/TEL-AML1 fusion protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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