Document Detail


Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia.
MedLine Citation:
PMID:  23378057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
LIM domain only 2 (Lmo2) is frequently deregulated in sporadic and gene therapy-induced acute T-cell lymphoblastic leukemia (T-ALL) where its overexpression is an important initiating mutational event. In transgenic and retroviral mouse models, Lmo2 expression can be enforced in multiple hematopoietic lineages but leukemia only arises from T cells. These data suggest that Lmo2 confers clonal growth advantage in T-cell progenitors. We analyzed proliferation, differentiation, and cell death in CD2-Lmo2 transgenic thymic progenitor cells to understand the cellular effects of enforced Lmo2 expression. Most impressively, Lmo2 transgenic T-cell progenitor cells were blocked in differentiation, quiescent, and immortalized in vitro on OP9-DL1 stromal cells. These cellular effects were concordant with a transcriptional signature in Lmo2 transgenic T-cell progenitor cells that is also present in hematopoietic stem cells (HSCs) and early T-cell precursor ALL. These results are significant in light of the crucial role of Lmo2 in the maintenance of the HSC. The cellular effects and transcriptional effects have implications for LMO2-dependent leukemogenesis and the treatment of LMO2-induced T-ALL.
Authors:
Susan M Cleveland; Stephen Smith; Rati Tripathi; Elizabeth M Mathias; Charnise Goodings; Natalina Elliott; Dunfa Peng; Wael El-Rifai; Dajun Yi; Xi Chen; Liqi Li; Charles Mullighan; James R Downing; Paul Love; Utpal P Davé
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  31     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2014-05-02     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  882-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 AlphaMed Press.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / biosynthesis*,  genetics
Animals
Cell Differentiation / physiology
Cell Lineage
Gene Expression
Hematopoietic Stem Cells / cytology*,  metabolism,  pathology
LIM Domain Proteins / biosynthesis*,  genetics
Leukemia, T-Cell / metabolism,  pathology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Precursor Cells, T-Lymphoid / cytology*,  pathology
Grant Support
ID/Acronym/Agency:
DK058404/DK/NIDDK NIH HHS; K08 HL089403/HL/NHLBI NIH HHS; K08HL089403/HL/NHLBI NIH HHS; P30 CA68485/CA/NCI NIH HHS; P30 CA68485)/CA/NCI NIH HHS; R25 GM062459/GM/NIGMS NIH HHS; T32 CA009592/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/LIM Domain Proteins; 0/Lmo2 protein, mouse
Comments/Corrections

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


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