Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia

Nakase, Koichi; Ishimaru, Fumihiko; Fujii, Keiko; Tabayashi, Takayuki; Kozuka, Teruhiko; Sezaki, Nobuo; Matsuo, Yoshinobu; Harada, Mine

doi:10.1016/s0301-472x(01)00796-2

Cited by 36 publications

(41 citation statements)

References 17 publications

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“…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). One of these products (from patient ID no.…”

Section: Novel Isoforms Of Ikzf2mentioning

confidence: 67%

“…31 A cDNA encoding a truncated, dominant-negative form of IKZF2 with impaired DNA-binding activity has been associated with adult T-cell leukemia or lymphoma 23 and T-cell acute lymphoblastic leukemia. 24 The development of T-cell lymphoma in mice expressing this dominant-negative form of IKZF2 provided further support for its clinical relevance. 31 Although the structure of our isoform of IKZF2 is different from that of the previously described short one, which lacks the second to fourth zinc-finger domains, 23 both forms have only one zinc-finger domain in the N-terminal DNA-binding region of the protein.…”

Section: Discussionmentioning

confidence: 93%

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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: 67%

Section: Discussionmentioning

confidence: 93%

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 presence of the alternative splice Helios variants was first revealed in research studies utilizing the primary leukemic cells from patients with newly diagnosed ALL (12)(13)(14). In this study, we observed that dominant-negative Helios-Δ326-1431 potentially induces the expression of several oncogenes.…”

Section: Discussionmentioning

confidence: 78%

“…In contrast, the T-cell malignancies were only observed in the gene-targeted mice of Ikaros (30). The related gene Helios has been shown to frequently exhibit multiple dominant-negative isoforms in patients with T-cell acute leukemia (6,(11)(12)(13)(14). In the mouse model, the overexpression of the artificial dominant-negative Helios isoform leads to increased T-cell proliferation, as well as the development of T-cell lymphomas (31).…”

Section: Discussionmentioning

confidence: 99%

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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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Lymphoid Malignancies

Teitell

Pandolfi

2004

Mouse Models of Human Cancer

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Malignant transformation may occur at any point during lymphoid cell maturation, resulting in stage‐ and lineage‐specific cancers of the immune system. Many in‐bred and engineered mouse strains develop specific lymphoid cancers, providing potentially useful models of human malignancy with insight for pathogenetic mechanisms. Newer techniques, targeting dysregulated gene expression to specific developmental stages portend newer, more accurate mouse models in the future. These models will likely have an increasing role in evaluating targeted therapeutic strategies for efficacy.

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Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia

Cited by 36 publications

References 17 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

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

Lymphoid Malignancies

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