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New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma
Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572011/ https://www.ncbi.nlm.nih.gov/pubmed/37830594 http://dx.doi.org/10.3390/cells12192381 |
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author | Velatooru, Loka Reddy Hu, Cheng Hui Bijani, Pedram Wang, Xiaohong Bojaxhi, Pierr Chen, Hao Duvic, Madeleine Ni, Xiao |
author_facet | Velatooru, Loka Reddy Hu, Cheng Hui Bijani, Pedram Wang, Xiaohong Bojaxhi, Pierr Chen, Hao Duvic, Madeleine Ni, Xiao |
author_sort | Velatooru, Loka Reddy |
collection | PubMed |
description | Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays were conducted in two CTCL cell lines (MJ cells and HH cells) by RNA interference and/or CRISPR/Cas9 gene editing. SS patients expressed heterogeneous levels of a new JAK3-INSL3 fusion transcript. Patients with high-level expression of JAK3-INSL3 showed poorer 5-year survival (n = 19, 42.1%) than patients with low-level expression (n = 14, 78.6%). CTCL cells transduced with specific shRNAs or sgRNAs had decreased new JAK3-INSL3 fusion transcript expression, reduced cell proliferation, and decreased colony formation. In NSG xenograft mice, smaller tumor sizes were observed in MJ cells transduced with specific shRNAs than cells transduced with controls. Our results suggest that the newly identified JAK3-INSL3 fusion transcript confers an oncogenic event in CTCL. |
format | Online Article Text |
id | pubmed-10572011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105720112023-10-14 New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma Velatooru, Loka Reddy Hu, Cheng Hui Bijani, Pedram Wang, Xiaohong Bojaxhi, Pierr Chen, Hao Duvic, Madeleine Ni, Xiao Cells Article Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays were conducted in two CTCL cell lines (MJ cells and HH cells) by RNA interference and/or CRISPR/Cas9 gene editing. SS patients expressed heterogeneous levels of a new JAK3-INSL3 fusion transcript. Patients with high-level expression of JAK3-INSL3 showed poorer 5-year survival (n = 19, 42.1%) than patients with low-level expression (n = 14, 78.6%). CTCL cells transduced with specific shRNAs or sgRNAs had decreased new JAK3-INSL3 fusion transcript expression, reduced cell proliferation, and decreased colony formation. In NSG xenograft mice, smaller tumor sizes were observed in MJ cells transduced with specific shRNAs than cells transduced with controls. Our results suggest that the newly identified JAK3-INSL3 fusion transcript confers an oncogenic event in CTCL. MDPI 2023-09-29 /pmc/articles/PMC10572011/ /pubmed/37830594 http://dx.doi.org/10.3390/cells12192381 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Velatooru, Loka Reddy Hu, Cheng Hui Bijani, Pedram Wang, Xiaohong Bojaxhi, Pierr Chen, Hao Duvic, Madeleine Ni, Xiao New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title | New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title_full | New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title_fullStr | New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title_full_unstemmed | New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title_short | New JAK3-INSL3 Fusion Transcript—An Oncogenic Event in Cutaneous T-Cell Lymphoma |
title_sort | new jak3-insl3 fusion transcript—an oncogenic event in cutaneous t-cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572011/ https://www.ncbi.nlm.nih.gov/pubmed/37830594 http://dx.doi.org/10.3390/cells12192381 |
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