The ability of BCR/ABL oncoproteins to induce leukemic transformation of hematopoietic cells depends on their tyrosine kinase activity, which is essential for the recruitment and the activation of multiple pathways (i.e., MAPkinase, Jun Kinase, PI-3k) that transduce oncogenic signals. Some of these pathways are also required for the anti-apoptotic effect of BCR/ABL. The objective of this proposal is t to delineate mechanisms involved in the survival-promoting effect of BCR/ABL and to assess the contribution of anti-apoptotic pathways for the leukmogenic potential of BCR/ABL. To this purpose, we will investigate mechanisms whereby three anti-apoptotic pathways regulated by BCR/ABL (Akt and STAT5 activation, mitochondrial targeting of Raf-1) promote cell survival and contribute to leukemogenesis. These studies should lead to a better understanding of the role of anti-apoptotic mechanisms in BCR/ABL leukemogenesis and the potential development of anti-leukemia therapies interfering with BCR/ABL-regulated survival signals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA078890-01A1
Application #
6232079
Study Section
Subcommittee G - Education (NCI)
Project Start
1999-06-01
Project End
2002-05-31
Budget Start
Budget End
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
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