Document Detail


Gene expression profiles of infant acute lymphoblastic leukaemia and its prognostically distinct subsets.
MedLine Citation:
PMID:  20377589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study compared the gene expression profiles of primary leukaemic cells from infants versus children with acute lymphoblastic leukaemia (ALL). Our analyses provided unprecedented evidence that remarkably different pathognomonic transcriptomes dominate the biology of infant versus paediatric high risk ALL. The genetic signature of infant ALL is characterized by concomitant overexpression of mitogenic and anti-apoptotic genes, some of which have been associated with early relapse in ALL. Our study demonstrated that primary leukaemia cells from infant ALL patients expressed significantly higher levels of genes for cytokines that mediate their biological effects through stimulation of the JAK-STAT signal transduction pathway including interleukin 1a, interleukin 1b, interleukin 2, and interleukin 7. We further showed that the JAK/STAT signalling pathway is constitutively active in CD10(-) infant ALL cells and treatment with a JAK3 inhibitor or a pan-JAK kinase inhibitor effectively triggered their apoptosis. These findings identified JAK3 as an attractive molecular target for disrupting the constitutively deregulated anti-apoptotic STAT3 and STAT5 signalling pathways in infant ALL cells.
Authors:
Sanjive Qazi; Fatih M Uckun
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-04
Journal Detail:
Title:  British journal of haematology     Volume:  149     ISSN:  1365-2141     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-06     Completed Date:  2010-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  865-73     Citation Subset:  IM    
Affiliation:
Molecular Oncology and Drug Discovery Program, Parker Hughes Institute, St. Paul, MN, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Antigens, Neoplasm / analysis
Apoptosis / genetics
Child
Child, Preschool
Gene Expression Profiling / methods
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Humans
Infant
Janus Kinase 3 / biosynthesis,  genetics
Neoplasm Proteins / biosynthesis,  genetics
Neprilysin / analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  metabolism
Prognosis
Signal Transduction / genetics
Up-Regulation
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/JAK3 protein, human; 0/Neoplasm Proteins; EC 2.7.10.1/Janus Kinase 3; EC 3.4.24.11/Neprilysin

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