Journal
BLOOD CANCER JOURNAL
Volume 1, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bcj.2011.30
Keywords
CML; PI3K inhibitors; mTORC1/2; targeted leukemia therapy
Categories
Funding
- NRSA, National Cancer Institute [F32CA154237]
- NIH [CA112325, R01CA137195]
- American Cancer Society [02-196]
- Concern Foundation
- Gibson Foundation
- Leukemia Texas Inc.
- Cancer Prevention and Research Institute of Texas [RP100402]
Ask authors/readers for more resources
The BCR/ABL tyrosine kinase promotes leukemogenesis through activation of several targets that include the phosphoinositide 3-kinase (PI3K). Tyrosine kinase inhibitors (TKIs), which target BCR/ABL, induce striking clinical responses. However, therapy with TKIs is associated with limitations such as drug intolerance, inability to universally eradicate the disease and emergence of BCR/ABL drug-resistant mutants. To overcome these limitations, we tested whether inhibition of the PI3K/target of rapamycin (mTOR) signaling pathway has antileukemic effect in primary hematopoietic stem cells and BA/F3 cells expressing the BCR/ABL oncoprotein. We determined that dual inhibition of PI3K/mTOR causes growth arrest and apoptosis leading to profound antileukemic effects both in vitro and in vivo. We also established that pharmacologic inhibition of the mTORC1/mTORC2 complexes is sufficient to cause these antileukemic effects. Our results support the development of inhibitors of the mTORC1/2 complexes for the therapy of leukemias that either express BCR/ABL or display deregulation of the PI3K/mTOR signaling pathway. Blood Cancer Journal (2011) 1, e34; doi:10.1038/bcj.2011.30; published online 2 September 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available