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Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia

Sgueglia, Giulia ; Massaro, Crescenzo ; Muro, Annamaria ; Lettiero, Ida LU ; D’Agostino, Erika ; Favale, Gregorio ; Simonelli, Nicla ; Del Gaudio, Nunzio ; Carafa, Vincenzo and De Marchi, Tommaso LU , et al. (2026) In Cell Death and Disease 17(1).
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... (More)

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. (Figure presented.)

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Death and Disease
volume
17
issue
1
article number
344
publisher
Springer Nature
external identifiers
  • pmid:41872140
  • scopus:105034948134
ISSN
2041-4889
DOI
10.1038/s41419-026-08594-4
language
English
LU publication?
yes
id
04e447c9-6bbe-49de-8576-a701278fd413
date added to LUP
2026-06-10 08:46:57
date last changed
2026-06-11 03:00:03
@article{04e447c9-6bbe-49de-8576-a701278fd413,
  abstract     = {{<p>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. (Figure presented.)</p>}},
  author       = {{Sgueglia, Giulia and Massaro, Crescenzo and Muro, Annamaria and Lettiero, Ida and D’Agostino, Erika and Favale, Gregorio and Simonelli, Nicla and Del Gaudio, Nunzio and Carafa, Vincenzo and De Marchi, Tommaso and Rotili, Dante and Valente, Sergio and Mai, Antonello and Sbardella, Gianluca and De Simone, Mariacarla and Altucci, Lucia and Dell’Aversana, Carmela}},
  issn         = {{2041-4889}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{Cell Death and Disease}},
  title        = {{Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia}},
  url          = {{http://dx.doi.org/10.1038/s41419-026-08594-4}},
  doi          = {{10.1038/s41419-026-08594-4}},
  volume       = {{17}},
  year         = {{2026}},
}