Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Velatooru, Loka Reddy, Hu, Cheng Hui, Bijani, Pedram, Wang, Xiaohong, Bojaxhi, Pierr, Chen, Hao, Duvic, Madeleine, Ni, Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785120136252882944
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
work_keys_str_mv AT velatoorulokareddy newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT huchenghui newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT bijanipedram newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT wangxiaohong newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT bojaxhipierr newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT chenhao newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT duvicmadeleine newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma
AT nixiao newjak3insl3fusiontranscriptanoncogeniceventincutaneoustcelllymphoma