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

Li,Yinghui; Liu,Yanhua; Liu,Can; Liu,Fengyong; Dou,Daolei; Zheng,Wenjie; Liu,Wei; Liu,Feifei

doi:10.3892/ol.2018.8214

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

Authors:
- Yinghui Li
- Yanhua Liu
- Can Liu
- Fengyong Liu
- Daolei Dou
- Wenjie Zheng
- Wei Liu
- Feifei Liu
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Affiliations: Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, P.R. China, Department of Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Experimental Facility, State Key Laboratory of Medical Chemical Biology, Tianjin 300071, P.R. China, Technical Center for Safety of Industrial Products, Tianjin Entry‑Exit Inspection and Quarantine Bureau, Tianjin 300308, P.R. China
Published online on: March 8, 2018 https://doi.org/10.3892/ol.2018.8214
Pages: 6957-6966
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 Helios-Δ326-1431.

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