The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells
Authors
Zhang, HaojianPeng, Cong
Hu, Yiguo
Li, Huawei
Sheng, Zhi
Chen, Yaoyu
Sullivan, Con
Cerny, Jan
Hutchinson, Lloyd
Higgins, Anne
Miron, Patricia M.
Zhang, Xueqing
Brehm, Michael A.
Li, Dongguang
Green, Michael R.
Li, Shaoguang
UMass Chan Affiliations
Department of PediatricsDepartment of Pathology
Program in Molecular Medicine
Department of Medicine, Division of Hematology and Oncology
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2012-07-15Keywords
Leukemia, Myelogenous, Chronic, BCR-ABL PositiveNeoplastic Stem Cells
Genes, Tumor Suppressor
Cancer Biology
Genetics and Genomics
Metadata
Show full item recordAbstract
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 the 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 downregulates the Blk gene (encoding B-lymphoid kinase) through c-Myc in leukemic 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 the proliferation of human CML stem cells. Our results show the feasibility of selectively targeting LSCs, an approach that should be applicable to other cancers.Source
Nat Genet. 2012 Jul 15;44(8):861-71. doi: 10.1038/ng.2350. Link to article on publisher's siteDOI
10.1038/ng.2350Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43993PubMed ID
22797726Notes
Co-author Haojian Zhang is a student in the Cancer Biology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ng.2350