The Philadelphia chromosome-positive (Ph+) leukemias, including chronic myeloid leukemia (CML) and Ph+ B- cell acute lymphoblastic leukemia (B-ALL), are prevalent blood cancers for which our current therapies are inadequate. While BCR-ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have replaced hematopoietic stem cell transplantation (HSCT) as initial therapy for CML, complete molecular remissions are rare and acquired resistance to TKI therapy is a significant clinical problem. Eligible Ph+ B-ALL patients undergo allogeneic HSCT in first remission following chemotherapy, but over half will relapse. Hence, it is likely that current therapy will not cure most Ph+ leukemia patients, and effective methods to eradicate residual leukemia are needed. To accomplish these goals, well-characterized mouse models of CML and B-ALL will be utilized to determine the mechanisms of pathogenesis of these diseases, to identify signaling pathways critical to leukemogenesis and to the genesis of leukemia-initiating or leukemia stem cels, and finally to validate these pathways as targets for therapy and conduct preclinical testing of molecularly targeted drugs. Together, these studies should yield important new knowledge that will improve the effectiveness of our current treatments for Ph+ leukemia, and increase the proportion of patients that are cured of their disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090576-13
Application #
8446337
Study Section
Special Emphasis Panel (ZRG1-BMCT-C (09))
Program Officer
Mufson, R Allan
Project Start
2001-04-01
Project End
2017-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
13
Fiscal Year
2013
Total Cost
$265,603
Indirect Cost
$98,557
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
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