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dc.contributor.authorJoshi, Ilaen_US
dc.contributor.authorYoshida, Toshimien_US
dc.contributor.authorJena, Nilamanien_US
dc.contributor.authorQi, Xiaoqingen_US
dc.contributor.authorZhang, Jiangwenen_US
dc.contributor.authorVan Etten, Richard A.en_US
dc.contributor.authorGeorgopoulos, Katiaen_US
dc.date.accessioned2015-08-03T14:01:23Z
dc.date.issued2014en_US
dc.identifier.citationJoshi, Ila, Toshimi Yoshida, Nilamani Jena, Xiaoqing Qi, Jiangwen Zhang, Richard A. Van Etten, and Katia Georgopoulos. 2014. “Ikaros mutation confers integrin-dependent pre-B cell survival and progression to acute lymphoblastic leukemia.” Nature immunology 15 (3): 294-304. doi:10.1038/ni.2821. http://dx.doi.org/10.1038/ni.2821.en
dc.identifier.issn1529-2908en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17820763
dc.description.abstractDeletion of the Ikaros (Ikzf1) DNA-binding domain generates dominant-negative isoforms that interfere with Ikaros family activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemias (B-ALL). Here, we show that conditional inactivation of the Ikaros DNA binding domain in early pre-B cells arrests their differentiation at a stage where integrin-dependent niche adhesion augments mitogen-activated protein kinase signaling, proliferation, and self-renewal, and attenuates pre-B cell receptor signaling and differentiation. Transplantation of polyclonal Ikzf1 mutant pre-B cells results in long-latency oligoclonal pre-B-ALL, demonstrating that loss of Ikaros contributes to multistep B-leukemogenesis. These results explain how normal pre-B cells transit from a highly proliferative and stromal-dependent to a stromal-independent phase where differentiation is enabled, providing potential therapeutic strategies for IKZF1 mutant B-ALL.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/ni.2821en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494688/pdf/en
dash.licenseLAAen_US
dc.titleIkaros mutation confers integrin-dependent pre-B cell survival and progression to acute lymphoblastic leukemiaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature immunologyen
dash.depositing.authorJoshi, Ilaen_US
dc.date.available2015-08-03T14:01:23Z
dc.identifier.doi10.1038/ni.2821*
dash.contributor.affiliatedJoshi, Ila
dash.contributor.affiliatedYoshida, Toshimi
dash.contributor.affiliatedGeorgopoulos, Katia


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