Document Detail

BCR-ABL-transformed GMP as myeloid leukemic stem cells.
MedLine Citation:
PMID:  19004799     Owner:  NLM     Status:  MEDLINE    
During blast crisis of chronic myelogenous leukemia (CML), abnormal granulocyte macrophage progenitors (GMP) with nuclear beta-catenin acquire self-renewal potential and may function as leukemic stem cells (Jamieson et al. N Engl J Med, 2004). To develop a mouse model for CML-initiating GMP, we expressed p210(BCR-ABL) in an established line of E2A-knockout mouse BM cells that retain pluripotency in ex vivo culture. Expression of BCR-ABL in these cells reproducibly stimulated myeloid expansion in culture and generated leukemia-initiating cells specifically in the GMP compartment. The leukemogenic GMP displayed higher levels of beta-catenin activity than either the nontransformed GMP or the transformed nonGMP, both in culture and in transplanted mouse BM. Although E2A-deficiency may have contributed to the formation of leukemogenic GMP, restoration of E2A-function did not reverse BCR-ABL-induced transformation. These results provide further evidence that BCR-ABL-transformed GMP with abnormal beta-catenin activity can function as leukemic stem cells.
Yosuke Minami; Scott A Stuart; Tomokatsu Ikawa; Yong Jiang; Asoka Banno; Irina C Hunton; Dennis J Young; Tomoki Naoe; Cornelis Murre; Catriona H M Jamieson; Jean Y J Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-11-11
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2008-12-17     Revised Date:  2009-11-23    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17967-72     Citation Subset:  IM    
Division of Hematology-Oncology, Department of Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093-0820, USA.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / deficiency,  metabolism
Cell Transformation, Neoplastic / pathology*
Cells, Cultured
Fusion Proteins, bcr-abl / metabolism*
Granulocyte-Macrophage Progenitor Cells / pathology*
Mice, Inbred C57BL
Models, Biological
Myeloid Progenitor Cells / pathology*
Neoplastic Stem Cells / pathology*
beta Catenin / metabolism
Grant Support
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Fusion Proteins, bcr-abl; 0/Tcf3 protein, mouse; 0/beta Catenin

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