Document Detail


Acute leukaemia in bcr/abl transgenic mice.
MedLine Citation:
PMID:  2179728     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Philadelphia chromosome, widely implicated in human leukaemia, is the result of a reciprocal translocation t(9;22) (q34;q11) in which the abl oncogene located at 9q34 is translocated to chromosome 22q11, where it is fused head-to-tail with 5' exons of the bcr gene. In acute lymphoblastic leukaemia, some patients have a breakpoint within the major breakpoint cluster region of the bcr gene, whereas others have the break within its first intron. This second type of translocation results in the transcription of a 7.0-kilobase chimaeric bcr/abl messenger RNA translated into a bcr/abl fusion protein, p190, which has an abnormal tyrosine kinase activity and is strongly autophosphorylated in vitro. We have generated mice transgenic for a bcr/abl p190 DNA construct and find that progeny are either moribund with, or die of acute leukaemia (myeloid or lymphoid) 10-58 days after birth. This finding is evidence for a causal relationship between the Philadelphia chromosome and human leukaemia.
Authors:
N Heisterkamp; G Jenster; J ten Hoeve; D Zovich; P K Pattengale; J Groffen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  344     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1990 Mar 
Date Detail:
Created Date:  1990-04-20     Completed Date:  1990-04-20     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  251-3     Citation Subset:  IM    
Affiliation:
Department of Pathology, Children's Hospital, Los Angeles, California 90027.
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / pathology
Bone Marrow / pathology
Cloning, Molecular
Leukemia, Experimental / genetics*
Leukemia, Myeloid, Acute / genetics,  pathology
Mice
Mice, Transgenic
Philadelphia Chromosome*
Phosphorylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics,  pathology
Protein-Tyrosine Kinases*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-abl
Proto-Oncogene Proteins c-bcr
RNA, Messenger / genetics
Recombinant Fusion Proteins / genetics
Transfection
Translocation, Genetic
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Recombinant Fusion Proteins; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/Proto-Oncogene Proteins c-abl; EC 2.7.11.1/Bcr protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-bcr

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


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