Document Detail


Diverse Mechanisms of mTOR Activation in Chronic and Blastic Phase of Chronic Myelogenous Leukemia.
MedLine Citation:
PMID:  23395818     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Chronic myelogenous leukemia (CML) is a stem cell disorder and leukemia stem cells (LSC) may contribute to the relapse of the disease. Quiescent LSCs are BCR-ABL independent, hence imatinib-resistant, therefore there is unmet need to identify new therapeutic targets in LSCs. Inhibition of the mammalian target of rapamycin (mTOR) in imatinib-resistant BCR-ABL1-positivecells was effective in vitro, but in clinical trials only 75% of patients responded to the treatment. Here we demonstrate, that mTOR activation in CML CD34+ progenitor cells is ERK-dependent in chronic phase of the disease, and ERK-independent in blast crisis. Rapamycin effectively inhibits mTOR in all phases of CML, but does not reduce number of LSCs-enriched CD34+ CML-BC cells, neither alone nor in combination with imatinib in CML-BC cells. These results show that potential therapeutic benefits of mTOR inhibition may be due to effects on differentiated leukemic cells and may be potentially achieved only in the chronic phase of the disease.
Authors:
Tomasz Stoklosa; Eliza Glodkowska-Mrowka; Grazyna Hoser; Magdalena Kielak; Ilona Seferynska; Pawel Wlodarski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-5
Journal Detail:
Title:  Experimental hematology     Volume:  -     ISSN:  1873-2399     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
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