Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin

Hahm, Kyungmin; Cobb, Bradley S.; McCarty, Aaron S.; Brown, Karen E.; Klug, Christopher A.; Lee, Robert; Akashi, Koichi; Weissman, Irving L.; Fisher, Amanda G.; Smale, Stephen T.

doi:10.1101/gad.12.6.782

Cited by 227 publications

(256 citation statements)

References 42 publications

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“…There was high expression of TCRgV9 and Vd2 that correlates with the high incidence of Vg9 and Vd2 usage reported previously in nasal T-cell lymphoma and chronic EBV infection. 26 We also observed higher expression of IKZF2 (P ¼ 0.0001), a T-cell-restricted IKAROS family member, 27 and T-cell adaptor protein SH2B3 (LNK, P ¼ 0.008) 28 and a repertoire of transcripts encoding KIR molecules (Supplementary Table 2). The analysis indicated that this group of cases was T-cell lymphomas expressing the gd TCR.…”

Section: Molecular Features Of Nk-cell and CD T-cell Lymphoma J Iqbalmentioning

confidence: 86%

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

et al. 2010

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Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic cd T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro Natural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Geneexpression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/ leukemia patients, 17 NK-and T-cell lines and 5 indolent NK-cell large-granular-lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of cd-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These cd-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (ab)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of cd T cells. They showed distinct expression of Vc9, Vd2 transcripts and were positive for TCRc, but negative for TCRb by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies.

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Section: Molecular Features Of Nk-cell and CD T-cell Lymphoma J Iqbalmentioning

confidence: 86%

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

et al. 2010

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“…The functional significance of the localization of TLX1 to the heterochromatic compartment is unclear at present. Such localization is not novel, having been previously reported for a number of mammalian transcriptional regulators including Ikaros, 38,39 Helios, 44 C/EBP, 45 NF-E2, 46 KRAZ-KAP1, 47 HSF1 48 and YY1. 49 One possibility is that TLX1 function at centromeric foci may be independent of its putative function as a regulator of euchromatic target genes.…”

Section: Discussionmentioning

confidence: 95%

The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells

et al. 2005

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“…1A; Georgopoulos et al 1992;Hahm et al 1994Hahm et al , 1998Morgan et al 1997;Kelley et al 1998;Honma et al 1999). The IKAROS family members encode proteins that are structurally and functionally similar.…”

Section: Structure and Function Of The Ikaros Gene Familymentioning

confidence: 99%

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

Georgopoulos

2017

Genes Dev.

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Lymphocyte differentiation is set to produce myriad immune effector cells with the ability to respond to multitudinous foreign substances. The uniqueness of this developmental system lies in not only the great diversity of cellular functions that it can generate but also the ability of its differentiation intermediates and mature effector cells to expand upon demand, thereby providing lifelong immunity. Surprisingly, the goals of this developmental system are met by a relatively small group of DNA-binding transcription factors that work in concert to control the timing and magnitude of gene expression and fulfill the demands for cellular specialization, expansion, and maintenance. The cellular and molecular mechanisms through which these lineage-promoting transcription factors operate have been a focus of basic research in immunology. The mechanisms of development discerned in this effort are guiding clinical research on disorders with an immune cell base. Here, I focus on IKAROS, one of the earliest regulators of lymphoid lineage identity and a guardian of lymphocyte homeostasis.

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Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin

Cited by 227 publications

References 42 publications

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells

The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma

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