CLL is the most common leukaemia in adults, and it exhibits a highly variable course. While some patients manage to keep the disease under control for years, others develop more aggressive forms that require early treatment. Despite the important advances made with treatments such as Bruton's tyrosine kinase (BTKi) inhibitors, such as ibrutinib, a number of patients end up developing resistance and suffering relapses.
The study was led by Lluís Hernández, from the Molecular pathology of lymphoid neoplasms research group at IDIBAPS, within the framework of the Clínic Barcelona Comprehensive Cancer Centre, with the participation of Elias Campo, head of the research group, and Valter Gattei's group, from the Centro di Referencia Oncologico in Aviano (Italy).
To identify new mechanisms of resistance, the team analysed the expression of coding and non-coding RNAs in several independent cohorts of patients with CLL. They focused especially on long non-coding RNAs, molecules that do not produce proteins but that regulate the activity of numerous genes involved in tumoral progression.
The analysis made it possible to identify three particularly relevant RNAs. Among them, LINC00152 stood out for its strong biological and clinical impact. Patients with high levels of this molecule had a more aggressive evolution of the disease and needed treatment before the rest.
"Our results indicate that LINC00152 is not only a marker associated with more aggressive forms of this lymphoid neoplasia, but that it could actively participate in the mechanisms that enable tumour cells to escape the effect of treatments," explains Lluís Hernández.
The study also showed that LINC00152 is especially abundant in cells with greater proliferative capacity, including in patients with BTK or PLCG2 mutations, alterations closely related to BTKi resistance. In addition, functional experiments showed that its blockade could reduce the growth of leukaemia cells from relapsed patients, even in the presence of ibrutinib.
"These results suggest new therapeutic strategies aimed at non-coding RNAs that could complement current treatments and offer alternatives to patients who relapse, with the ultimate goal of improving disease control and quality of life for affected people," adds Lluís Hernández.
Study of reference
Bittolo, T., Bomben, R., Martínez-Muñoz, C. et al. LINC00152 is a lncRNA modulated by microenvironmental stimuli that has pathogenetic and clinical relevance in CLL. Sci Rep (2026). https://doi.org/10.1038/s41598-026-68193-3
