Acute Leukaemia in bcr/abl Transgenic Mice

Nature. 1990 Mar 15;344(6263):251-3. doi: 10.1038/344251a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / pathology
  • Bone Marrow / pathology
  • Cloning, Molecular
  • Leukemia, Experimental / genetics*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Mice, Transgenic
  • Philadelphia Chromosome*
  • Phosphorylation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / 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

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl
  • Bcr protein, mouse
  • Proto-Oncogene Proteins c-bcr