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Medline ® Abstract for Reference 224

of '慢性髓系白血病的细胞和分子生物学'

224
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Acute leukaemia in bcr/abl transgenic mice.
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Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J
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Nature. 1990;344(6263):251.
 
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.
AD
Department of Pathology, Children's Hospital, Los Angeles, California 90027.
PMID