Reduced oncogenicity of p190 Bcr/Abl F-actin-binding domain mutants.

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

Blood

journal_title

Blood

authors

Heisterkamp N,Voncken JW,Senadheera D,Gonzalez-Gomez I,Reichert A,Haataja L,Reinikainen A,Pattengale PK,Groffen J

subject

Has Abstract

pub_date

2000-09-15 00:00:00

pages

2226-32

issue

6

eissn

0006-4971

issn

1528-0020

journal_volume

96

pub_type

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