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International Journal of Hematology

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01.09.2014 | Progress in Hematology

Ikaros fingers on lymphocyte differentiation

verfasst von: Toshimi Yoshida, Katia Georgopoulos

Erschienen in: International Journal of Hematology | Ausgabe 3/2014

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Abstract

The Ikaros family of DNA-binding proteins are critical regulators of lymphocyte differentiation. In multipotent, hematopoietic progenitors, Ikaros supports transcriptional priming of genes promoting lymphocyte differentiation. Ikaros targets the Nucleosome Remodeling Deacetylase (NuRD) complex to lymphoid lineage genes, thereby increasing chromatin accessibility and transcriptional priming. After lymphoid lineage specification, Ikaros expression is raised to levels characteristic of intermediate B cell and T cell precursors, which is necessary to support maturation and prevent leukemogenesis. Loss of Ikaros in T cell precursors allows the NuRD complex to repress lymphocyte genes and extends its targeting to genes that support growth and proliferation, causing their activation and triggering a cascade of events that leads to leukemogenesis. Loss of Ikaros in B cell precursors blocks differentiation and perpetuates stromal adhesion by enhancing integrin signaling. The combination of integrin and cytokine signaling in Ikaros-deficient pre-B cells promotes their survival and self-renewal. The stages of lymphocyte differentiation that are highly dependent on Ikaros are underscored by changes in Ikaros transcription, supported by a complex network of stage-specific regulatory networks that converge upon the Ikzf1 locus. It is increasingly apparent that understanding the regulatory networks that operate upstream and downstream of Ikaros is critical not only for our understanding of normal lymphopoiesis, but also in placing the right finger on the mechanisms that support hematopoietic malignancies in mouse and human.

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Titel: Ikaros fingers on lymphocyte differentiation
verfasst von: Toshimi Yoshida
Katia Georgopoulos
Publikationsdatum: 01.09.2014
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 3/2014
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-014-1644-5

Springer Medizin

Ikaros fingers on lymphocyte differentiation

Abstract

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