Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors

Kelley, Clair M.; Ikeda, Tohru; Koipally, Joseph; Avitahl, Nicole; Wu, Li; Georgopoulos, Katia; Morgan, Bruce

doi:10.1016/s0960-9822(98)70202-7

Cited by 213 publications

(211 citation statements)

References 34 publications

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“…IKZF2 belongs to the IKAROS family of transcriptional factors, which are important regulators of lymphocyte development, 21,22 and short isoforms of IKZF2 have been reported for the malignant cells of adult T-cell leukemia or lymphoma 23 and T-cell acute lymphoblastic leukemia. 24 In our cohort, RT-PCR amplification of the entire coding region of the IKZF2 mRNA detected a product in five of the seven study subjects with LOH at the IKZF2 locus (Figure 4a).…”

Section: Novel Isoforms Of Ikzf2mentioning

confidence: 99%

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Yamashita

Nakamura

et al. 2008

Leukemia

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Angioimmunoblastic T-cell lymphoma (AILT) and peripheral T-cell lymphoma, unspecified (PTCL-u) are relatively frequent subtypes of T-or natural killer cell lymphoma. To characterize the structural anomalies of chromosomes associated with these disorders, we here determined chromosome copy number alterations (CNAs) and loss of heterozygosity (LOH) at 455 000 single nucleotide polymorphism loci for clinical specimens of AILT (n ¼ 40) or PTCL-u (n ¼ 33). Recurrent copy number gain common to both conditions was detected on chromosomes 8, 9 and 19, whereas common LOH was most frequent for a region of chromosome 2. AILT-or PTCL-uspecific CNAs or LOH were also identified at 21 regions, some spanning only a few hundred base pairs. We also identified prognosis-related CNAs or LOH by several approaches, including Cox's proportional hazard analysis. Among the genes that mapped to such loci, a poor prognosis was linked to overexpression of CARMA1 at 7p22 and of MYCBP2 at 13q22, with both genes being localized within regions of frequent copy number gain. For a frequent LOH region at 2q34, we also identified IKAROS family zinc-finger 2 cDNAs encoding truncated proteins. Our data indicate that AILT and PTCL-u consist of heterogeneous subgroups with distinct transforming genetic alterations.

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Section: Novel Isoforms Of Ikzf2mentioning

confidence: 99%

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Yamashita

Nakamura

et al. 2008

Leukemia

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“…The Nalm-6 cells of the UT, Lenti-GFP and Lenti-Aiolos groups were seeded into 24-well plates (Corning Costar) in triplicate at a density of 2x10 5 per well at 37˚C seven days after transfection. The number of live cells was determined by trypan blue staining (Sigma-Aldrich) and was measured daily for 5 days using a haemocytometer (Jingmai Biotech., Ji'nan, China) under an inverted microscope (IX71; Olympus Corp., Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Numerous transcriptional regulators have critical functions in this malignant process and may regulate the expression of genes, whose products affect the fate and function of lymphoid cells (3). The Ikaros family of proteins is an example of these factors (4), which encode zinc-finger DNA-binding proteins (5)(6)(7). Aiolos, the second Ikaros family member identified, is of particular interest in the investigation of BCP-ALL (6).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Aiolos in Nalm-6 acute lymphoblastic leukaemia cells reduces apoptosis by suppressing phosphatase and tensin homologue deleted on chromosome 10 and activating the phosphatidylinositol-3-kinase/Akt signalling pathway

Wang

Guo

et al. 2015

Molecular Medicine Reports

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Abstract. The aim of the present study was to elucidate the molecular mechanism of Aiolos in the regulation of B-cell leukaemia. A lentiviral system was used for overexpression of the Aiolos gene in Nalm-6 cells to determine the effects of Aiolos on proliferation, apoptosis and the cell cycle. The expression and activation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Akt were also investigated. Upregulation of Aiolos inhibited cell growth and arrested an increased number of Nalm-6 cells at the G0/G1 phase. The apoptotic cell quantities were also significantly lower in the Aiolos-transfected Nalm-6 cells. In addition, Aiolos overexpression downregulated PTEN, but increased the expression and phosphorylation of Akt in the Nalm-6 cells. The Akt inhibitor, Akti-1/2, reduced the percentage of viable Aiolos-overexpressed Nalm-6 cells, however, it had no effect on cell cycle arrest or proliferation. Aiolos upregulation in the Nalm-6 cells inhibited cell proliferation, suppressed apoptosis and arrested the cell cycle at the G0/G1 phase. Aiolos improved the survival of Nalm-6 cells via PTEN-and Akt-dependent processes.

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“…Significantly, these regulatory factors which control normal development are frequently disturbed, and also implicated in T-cell transformations and leukemia (2). Helios (Ikzf2), which is a zinc-finger DNA binding transcription factor and a key regulator of T-lineage differentiation, is a prime example (4,5). Helios belongs to the Ikaros transcription factor family, and shares a common structure, which is characterized by two zinc finger domains, an N-terminal DNA-binding domain (core motif GGGAA), and a C-terminal dimerization domain (4,6).…”

Section: Introductionmentioning

confidence: 99%

“…Helios (Ikzf2), which is a zinc-finger DNA binding transcription factor and a key regulator of T-lineage differentiation, is a prime example (4,5). Helios belongs to the Ikaros transcription factor family, and shares a common structure, which is characterized by two zinc finger domains, an N-terminal DNA-binding domain (core motif GGGAA), and a C-terminal dimerization domain (4,6). Helios is specifically expressed in the T-cell lineage from the early stages of development.…”

Section: Introductionmentioning

confidence: 99%

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Liu

et al. 2018

Oncol Lett

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Abstract. T-cell acute lymphoblastic leukemia is a hematopoietic malignant disease, which arises from a genetic defect in the T-cell maturation signaling pathway. As a result, it is necessary to identify the molecules that impact T-cell development and control lymphoid-lineage malignancy. The present study utilized Jurkat T lymphoblastic cells as a well-established approach for the investigation into the function of the non-canonical alternative splice variant of Helios for the in vitro study of T-cell differentiation and leukemogenesis. In the present study, the Jurkat T-cell lines with stable overexpression of the wild-type (Helios-1) or the non-canonical short isoform (Helios-Δ326-1431), were established. RNA microarray, reverse transcription-quantitative polymerase chain reaction and flow cytometry were used to assess changes in the gene expression profiles and to monitor the cell surface markers during T-cell differentiation. Multiple genes associated with T-cell differentiation and leukemogenesis were identified as being either activated or suppressed. In addition, the results indicated that the stable overexpression of the Helios isoforms stimulated the differentiation pathway of the T-lineage lymphoblastic cells. Therefore, these results suggest that full-length Helios-1 has a tumor suppressor-like and immunomodulatory role, in contrast to the oncogenic function of the non-canonical short isoform

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Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors

Cited by 213 publications

References 34 publications

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

Overexpression of Aiolos in Nalm-6 acute lymphoblastic leukaemia cells reduces apoptosis by suppressing phosphatase and tensin homologue deleted on chromosome 10 and activating the phosphatidylinositol-3-kinase/Akt signalling pathway

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

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