Year: 2026
Type: article
Abstract: Dysregulation of alternative splicing is increasingly associated with cancer development and tumor progression. BCL2-associated transcription factor 1 (BCLAF1) is involved in a wide range of biological processes and it is continuously being investigated due to its intricate function in tumorigenesis and drug resistance. In acute myeloid leukemia (AML) cell lines, we identified two distinct, unbalanced isoforms of BCLAF1: the full-length isoform, which exhibits oncogenic properties, and the short-length isoform, which seems to act as a tumor suppressor. Treatment with specific epidrugs can re-establish the physiological balance of full- and short-length isoforms, restoring their correct equilibrium. Our results suggest the existence of a newly identified mechanism underlying the regulation of BCLAF1 splicing orchestrated, at least in part, by the interplay between HDAC1 and DNMT3A, and directly correlated with the healthy or cancerous state of hematopoietic cells. Our findings shed light on a novel regulatory axis in AML and highlight the potential of epidrugs to restore normal splicing patterns, paving the way for innovative therapies.
Source: Cell Death and Disease
Authors: Giulia Sgueglia, Crescenzo Massaro, Annamaria Muro, Ida Lettiero, Erika D’Agostino, Gregorio Favale, Nicla Simonelli, Nunzio Del Gaudio, Vincenzo Carafa, Tommaso De Marchi, Dante Rotili, Sergio Valente, Antonello Mai, Gianluca Sbardella, Mariacarla De Simone, Lucia Altucci, Carmela Dell’Aversana
Institutions: University of Campania "Luigi Vanvitelli", Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Link Campus University, Biogem, Lund University, Roma Tre University, Istituto Nazionale Biostrutture e Biosistemi, Sapienza University of Rome, University of Salerno, Ospedale Antonio Cardarelli, Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli, LUM Jean Monnet University, National Research Council
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
Awards: G1285910477, G850769058
OpenAlex ID: W7140216202