|  Help  |  About  |  Contact Us

Publication : Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice.

First Author  Hu Y Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  45 Pages  16870-5
PubMed ID  17077147 Mgi Jnum  J:117101
Mgi Id  MGI:3695619 Doi  10.1073/pnas.0606509103
Citation  Hu Y, et al. (2006) Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci U S A 103(45):16870-5
abstractText  It is generally believed that shutting down the kinase activity of BCR-ABL by imatinib will completely inhibit its functions, leading to inactivation of its downstream signaling pathways and cure of the disease. Imatinib is highly effective at treating human Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but not Ph(+) B cell acute lymphoblastic leukemia (B-ALL) and CML blast crisis. We find that SRC kinases activated by BCR-ABL remain fully active in imatinib-treated mouse leukemic cells, suggesting that imatinib does not inactivate all BCR-ABL-activated signaling pathways. This SRC pathway is essential for leukemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis. Inhibition of both SRC and BCR-ABL kinase activities by dasatinib affords complete B-ALL remission. However, curing B-ALL and CML mice requires killing leukemic stem cells insensitive to both imatinib and dasatinib. Besides BCR-ABL and SRC kinases, stem cell pathways must be targeted for curative therapy of Ph(+) leukemia.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

0 Bio Entities

0 Expression