# Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia

## TL;DR

This study explores how splicing of the BCLAF1 gene is regulated in acute myeloid leukemia and how epidrugs can restore normal splicing patterns.

## Contribution

The paper identifies a novel regulatory mechanism involving HDAC1 and DNMT3A in BCLAF1 splicing in AML.

## Key findings

- Two distinct BCLAF1 isoforms were identified in AML cell lines, with opposing oncogenic and tumor suppressor roles.
- Epidrug treatment can restore the balance between BCLAF1 isoforms.
- HDAC1 and DNMT3A interplay regulates BCLAF1 splicing in hematopoietic cells.

## 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.