LINC00152 is a lncRNA modulated by microenvironmental stimuli that has pathogenetic and clinical relevance in CLL

Abstract Chronic lymphocytic leukemia (CLL) is a common lymphoid neoplasm with heterogeneous biological features and clinical behavior, influenced by acquired genetic alterations and microenvironment interactions. We explored non-coding RNAs expression to understand their role in CLL pathogenesis and identify new clinically relevant biological biomarkers that could improve CLL prognosis and management. We initially profiled coding and non-coding RNA families in different CLL cohorts (N = 21) to identify those modulated by a combination of agonist microenvironment stimuli. Then we focused on lncRNAs that were overexpressed in response to the agonist stimuli, even in the presence of Ibrutinib, and whose baseline expression was associated with a shorter time-to-treatment in an independent CLL series (N = 266). Three lncRNAs ( LINC00152 , LINC00158 and RP11-161H23.5 ) were selected for functional validations in MEC-1 CLL cell line, where they demonstrated to regulate genes and pathways activated by microenvironmental stimuli, including induction of miR-155, a key oncomiR also enhanced by agonist treatment. LINC00152 expression was associated with proxies of microenvironment stimulation in vivo, and its silencing ex vivo reduced cell growth under combined microenvironmental stimulation and Ibrutinib in a subset of Ibrutinib-relapsed primary CLL samples, underscoring its potential relevance for further studies to improve CLL therapy.

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Publication Details

Journal
Scientific Reports
Published
2026-08-26
DOI
https://doi.org/10.1038/s41598-026-68193-3
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
0.00

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article

LINC00152 is a lncRNA modulated by microenvironmental stimuli that has pathogenetic and clinical relevance in CLL

Thorsten Zenz, R. Bomben, Luís Hernández, Amani Dhiflaoui et al.
Scientific Reports
Chronic Lymphocytic Leukemia Research
article

LINC00152 is a lncRNA modulated by microenvironmental stimuli that has pathogenetic and clinical relevance in CLL

Thorsten Zenz, R. Bomben, Luís Hernández, Amani Dhiflaoui, Federico Pozzo, Robel Papotti, Virginia Amador, Ruslana Shadrina, Tamara Bittolo, Filippo Vit, Ferran Nadeu, Cristina Martínez-Muñoz, Dolors Colomer, Patricia Fernández-Guzmán, Blanca De Moner, Dario Rafael Romero, Ares Martínez-Farran, Ariadna Giró, Ian Márquez-López, Juan A. Piñeyroa, Ruth Orellana, Valter Gattei, Elias Campo, Julio Delgado, Sílvia Beà, Núria Vilardell-Timoneda
article en

Abstract

Abstract Chronic lymphocytic leukemia (CLL) is a common lymphoid neoplasm with heterogeneous biological features and clinical behavior, influenced by acquired genetic alterations and microenvironment interactions. We explored non-coding RNAs expression to understand their role in CLL pathogenesis and identify new clinically relevant biological biomarkers that could improve CLL prognosis and management. We initially profiled coding and non-coding RNA families in different CLL cohorts (N = 21) to identify those modulated by a combination of agonist microenvironment stimuli. Then we focused on lncRNAs that were overexpressed in response to the agonist stimuli, even in the presence of Ibrutinib, and whose baseline expression was associated with a shorter time-to-treatment in an independent CLL series (N = 266). Three lncRNAs ( LINC00152 , LINC00158 and RP11-161H23.5 ) were selected for functional validations in MEC-1 CLL cell line, where they demonstrated to regulate genes and pathways activated by microenvironmental stimuli, including induction of miR-155, a key oncomiR also enhanced by agonist treatment. LINC00152 expression was associated with proxies of microenvironment stimulation in vivo, and its silencing ex vivo reduced cell growth under combined microenvironmental stimulation and Ibrutinib in a subset of Ibrutinib-relapsed primary CLL samples, underscoring its potential relevance for further studies to improve CLL therapy.

Scientific Reports
Hospital de Sant Pau (ES), University Hospital of Zurich (CH), Centro di Riferimento Oncologico (IT), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Universitat de Barcelona (ES)
AstraZeneca, Fundació la Marató de TV3, “la Caixa” Foundation, Generalitat de Catalunya, Ministero della Salute, Centro de Investigación Biomédica en Red de Cáncer, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, Agència de Gestió d'Ajuts Universitaris i de Recerca, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 85%
Chronic Lymphocytic Leukemia Research
DOIOpen Access PDFOpenAlex
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