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Medline ® Abstract for Reference 226

of 'Cellular and molecular biology of chronic myeloid leukemia'

Human bcr-abl gene has a lethal effect on embryogenesis.
Heisterkamp N, Jenster G, Kioussis D, Pattengale PK, Groffen J
Transgenic Res. 1991;1(1):45.
The chimaeric bcr-abl oncogene is thought to have a crucial role in the development or maintenance of chronic myelogenous leukaemia. To study this oncogene in a more direct way, the bcr-abl gene encoding the P210 protein under control of the bcr gene promoter was introduced into fertilized one-cell embryos, which were then re-implanted into foster mothers. Our data, obtained after several experiments, demonstrate that no live transgenic progeny could be obtained using this bcr-abl construct. The bcr gene is expressed in the course of embryogenesis and the bcr-abl gene product appears to have a pleiotropic lethal effect during this period of development. In concordance, several gross abnormalities were observed while no evidence of neoplastic formation was found. These results suggest that the bcr-abl encoded protein severely affects the process of normal embryogenesis.
Section of Molecular Diagnosis, Childrens Hospital of Los Angeles, CA 90027.