The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells

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Author
Peng, Cong
Li, Huawei
Sheng, Zhi
Chen, Yaoyu
Sullivan, Con
Cerny, Jan
Hutchinson, Lloyd
Higgins, Anne
Miron, Patricia
Zhang, Xueqing
Brehm, Michael
Li, Dongguang
Green, Michael R.
Li, Shaoguang
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.2350Metadata
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Zhang, Haojian, Cong Peng, Yiguo Hu, Huawei Li, Zhi Sheng, Yaoyu Chen, Con Sullivan, et al. 2012. The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells. Nature genetics 44(8): 861-871.Abstract
A therapeutic strategy for treating cancer is to target and eradicate cancer stem cells (CSCs) without harming their normal stem cell counterparts. The success of this approach relies on identification of molecular pathways that selectively regulate CSC function. Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for CSCs, we show that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene through c-Myc in leukemia stem cells (LSCs) in CML mice and that Blk functions as a tumor suppressor in LSCs but does not affect normal hematopoietic stem cells (HSCs) or hematopoiesis. Blk suppresses LSC function through a pathway involving an upstream regulator, Pax5, and a downstream effector, p27. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. Blk also suppresses human CML stem cells. Our results demonstrate the feasibility of selectively targeting LSCs, an approach that should be applicable to other cancers.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408839/pdf/Terms of Use
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