Abstract:
:The deregulated Bcr/Abl tyrosine kinase is responsible for the development of Philadelphia (Ph)-positive leukemia in humans. To investigate the significance of the C-terminal Abl actin-binding domain within Bcr/Abl p190 in the development of leukemia/lymphoma in vivo, mutant p190 DNA constructs were used to generate transgenic mice. Eight founder and progeny mice of 5 different lines were monitored for leukemogenesis. Latency was markedly increased and occurrence decreased in the p190 del C lines as compared with nonmutated p190 BCR/ABL transgenics. Western blot analysis of involved hematologic tissues of the p190 del C transgenics with end-stage disease showed high-level expression of the transgene and tyrosine phosphorylation of Cbl and Hef1/Cas, proteins previously shown to be affected by Bcr/Abl. These results show that the actin-binding domain of Abl enhances leukemia development but does not appear to be an absolute requirement for leukemogenesis.
journal_name
Bloodjournal_title
Bloodauthors
Heisterkamp N,Voncken JW,Senadheera D,Gonzalez-Gomez I,Reichert A,Haataja L,Reinikainen A,Pattengale PK,Groffen Jsubject
Has Abstractpub_date
2000-09-15 00:00:00pages
2226-32issue
6eissn
0006-4971issn
1528-0020journal_volume
96pub_type
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