2026-04-17T01:06:46Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2011802025-12-04T19:10:35Zcom_2072_1057col_2072_478858col_2072_478917

00925njm 22002777a 4500 dc Johansson, Patricia author Laguna, Teresa author Ossowski, Julio author Pancaldi, Vera author Brauser, Martina author Dührsen, Ulrich author Keuneke, Lara author Queirós, Ana C. author Richter, Julia author Martín-Subero, José Ignacio author Siebert, Reiner author Schlegelberger, Brigitte author Küppers, Ralf author Dürig, Jan author Murga Penas, Eva M. author Carillo de Santa Pau, Enrique author Bergmann, Anke K. author 2023-07-26T08:06:31Z 2023-07-26T08:06:31Z 2022-11-14 2023-07-20T10:04:46Z Background: The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor alpha beta-positive CD8(+) memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples. Results: We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation. Conclusions: DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed. Cèl·lules T Leucèmia T cells Leukemia Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker