Acute leukaemia in bcr/abl transgenic mice.
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.
Heisterkamp
N
N
Department of Pathology, Children's Hospital, Los Angeles, California 90027.
Jenster
G
G
ten Hoeve
J
J
Zovich
D
D
Pattengale
P K
PK
Groffen
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D003001:Cloning, Molecular; D007942:Leukemia, Experimental / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010677:Philadelphia Chromosome; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl; D051562:Proto-Oncogene Proteins c-bcr; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014162:Transfection; D014178:Translocation, Genetic
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr