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dc.contributor.authorHeidel, Florian H.en_US
dc.contributor.authorBullinger, Larsen_US
dc.contributor.authorArreba-Tutusaus, Patriciaen_US
dc.contributor.authorWang, Zhuen_US
dc.contributor.authorGaebel, Juliaen_US
dc.contributor.authorHirt, Carstenen_US
dc.contributor.authorNiederwieser, Dietgeren_US
dc.contributor.authorLane, Steven W.en_US
dc.contributor.authorDöhner, Konstanzeen_US
dc.contributor.authorVasioukhin, Valeraen_US
dc.contributor.authorFischer, Thomasen_US
dc.contributor.authorArmstrong, Scott A.en_US
dc.date.accessioned2014-02-18T18:11:28Z
dc.date.issued2013en_US
dc.identifier.citationHeidel, F. H., L. Bullinger, P. Arreba-Tutusaus, Z. Wang, J. Gaebel, C. Hirt, D. Niederwieser, et al. 2013. “The cell fate determinant Llgl1 influences HSC fitness and prognosis in AML.” The Journal of Experimental Medicine 210 (1): 15-22. doi:10.1084/jem.20120596. http://dx.doi.org/10.1084/jem.20120596.en
dc.identifier.issn0022-1007en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11717571
dc.description.abstractA unique characteristic of hematopoietic stem cells (HSCs) is the ability to self-renew. Several genes and signaling pathways control the fine balance between self-renewal and differentiation in HSCs and potentially also in leukemia stem cells. Recently, studies have shed light on developmental molecules and evolutionarily conserved signals as regulators of stem cells in hematopoiesis and leukemia. In this study, we provide evidence that the cell fate determinant Llgl1 (lethal giant larvae homolog 1) plays an important role in regulation of HSCs. Loss of Llgl1 leads to an increase in HSC numbers that show increased repopulation capacity and competitive advantage after transplantation. This advantage increases upon serial transplantation or when stress is applied to HSCs. Llgl1−/− HSCs show increased cycling but neither exhaust nor induce leukemia in recipient mice. Llgl1 inactivation is associated with transcriptional repression of transcription factors such as KLF4 (Krüppel-like factor 4) and EGR1 (early-growth-response 1) that are known inhibitors of HSC self-renewal. Decreased Llgl1 expression in human acute myeloid leukemia (AML) cells is associated with inferior patient survival. Thus, inactivation of Llgl1 enhances HSC self-renewal and fitness and is associated with unfavorable outcome in human AML.en
dc.language.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1084/jem.20120596en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549713/pdf/en
dash.licenseLAAen_US
dc.titleThe cell fate determinant Llgl1 influences HSC fitness and prognosis in AMLen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Experimental Medicineen
dash.depositing.authorBullinger, Larsen_US
dc.date.available2014-02-18T18:11:28Z
dc.identifier.doi10.1084/jem.20120596*
dash.authorsorderedfalse
dash.contributor.affiliatedBullinger, Lars


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