Document Detail


The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation.
MedLine Citation:
PMID:  20827285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The t(6;9)-positive acute myeloid leukemia (AML) is classified as a separate clinical entity because of its early onset and poor prognosis. The hallmark of t(6;9) AML is the expression of the DEK/CAN fusion protein. The leukemogenic potential of DEK/CAN has been called into question, because it was shown to be unable to block the differentiation of hematopoietic progenitors. We found that DEK/CAN initiated leukemia from a small subpopulation within the hematopoietic stem cell (HSC) population expressing a surface marker pattern of long-term (LT) HSC. The propagation of established DEK/CAN-positive leukemia was not restricted to the LT-HSC population, but occurred even from more mature and heterogeneous cell populations. This finding indicates that in DEK/CAN-induced leukemia, there is a difference between 'leukemia-initiating cells' (L-ICs) and 'leukemia-maintaining cells' (L-MCs). In contrast to the L-IC cells represented by a very rare subpopulation of LT-HSC, the L-MC seem to be represented by a larger and phenotypically heterogeneous cell population.
Authors:
C Oancea; B Rüster; R Henschler; E Puccetti; M Ruthardt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-09
Journal Detail:
Title:  Leukemia     Volume:  24     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-10     Completed Date:  2010-12-22     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1910-9     Citation Subset:  IM    
Affiliation:
Department of Hematology, Goethe University, Frankfurt, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Ly / genetics
Cell Differentiation
Colony-Forming Units Assay
DNA-Binding Proteins / genetics*
Female
Hematopoietic Stem Cells / cytology*,  drug effects,  physiology
Leukemia, Experimental / genetics
Leukemia, Myeloid, Acute / genetics*,  pathology
Membrane Proteins / genetics
Mice
Mice, Inbred C57BL
Mutagenesis, Site-Directed
Nuclear Pore Complex Proteins / genetics
Oncogene Proteins / genetics*
Open Reading Frames
Recombinant Fusion Proteins / pharmacology
Splenomegaly / pathology
Translocation, Genetic
Chemical
Reg. No./Substance:
0/Antigens, Ly; 0/DEK protein, mouse; 0/DNA-Binding Proteins; 0/Ly6a protein, mouse; 0/Membrane Proteins; 0/Nuclear Pore Complex Proteins; 0/Oncogene Proteins; 0/Recombinant Fusion Proteins

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


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