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dc.contributor.authorZhang, Haojian
dc.contributor.authorPeng, Cong
dc.contributor.authorHu, Yiguo
dc.contributor.authorLi, Huawei
dc.contributor.authorSheng, Zhi
dc.contributor.authorChen, Yaoyu
dc.contributor.authorSullivan, Con
dc.contributor.authorCerny, Jan
dc.contributor.authorHutchinson, Lloyd
dc.contributor.authorHiggins, Anne
dc.contributor.authorMiron, Patricia
dc.contributor.authorZhang, Xueqing
dc.contributor.authorBrehm, Michael
dc.contributor.authorLi, Dongguang
dc.contributor.authorGreen, Michael R.
dc.contributor.authorLi, Shaoguang
dc.date.accessioned2013-10-16T19:48:43Z
dc.date.issued2012
dc.identifier.citationZhang, 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.en_US
dc.identifier.issn1061-4036en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11179756
dc.description.abstractA 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.en_US
dc.language.isoen_USen_US
dc.relation.isversionofdoi:10.1038/ng.2350en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408839/pdf/en_US
dash.licenseLAA
dc.titleThe Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNature geneticsen_US
dash.depositing.authorHu, Yiguo
dc.date.available2013-10-16T19:48:43Z
dc.identifier.doi10.1038/ng.2350*
dash.authorsorderedfalse
dash.contributor.affiliatedZhang, Haojian
dash.contributor.affiliatedHu, Yiguo


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