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Background <p>Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), characterized by a fusion between the <i>PML</i> and <i>RARA</i> genes and by a block in the myeloid maturation at the promyelocytic stage.</p> Methods <p>This study investigates the epigenetic landscape of APL by integrating ChIP-seq data on eight histone modifications and RNA-seq in APL as well as non-APL AML. APL showed a distinct chromatin profile that differed from non-APL AML.</p> Results <p>We describe APL-specific changes in H3K27ac, H3K9me3, and H3K27me3 with impact on enhancer activity, repression of transposable elements, and Polycomb regulated gene repression. The APL-specific H3K27ac pattern identifies APL-specific enhancer and super-enhancer regions, including a subset of enhancers that are bound by the PML-RARA fusion protein. While chromatin bound specifically by PML-RARA were dominantly active, APL was also characterized by gain of APL-specific heterochromatin states with significant gains of H3K9me3 enriched lamina-associated domains and the transposable elements LINE, LTR, and SINE.</p> Conclusion <p>These findings suggest a unique enhancer and heterochromatin profile in APL, with implications for transcription regulation and treatment response. These findings offer novel insights into the pathogenesis of APL.</p>

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Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia

  • 期刊论文

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  • 发表日期：

    2025年10月30日

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  • Xiangfu Zhong,
  • Lina Cordeddu,
  • Angelica Gamboa-Cedeno,
  • Sofia Bengtzén,
  • Karl Ekwall,
  • Andreas Lennartsson,
  • Sören Lehmann

摘要

Background

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), characterized by a fusion between the PML and RARA genes and by a block in the myeloid maturation at the promyelocytic stage.

Methods

This study investigates the epigenetic landscape of APL by integrating ChIP-seq data on eight histone modifications and RNA-seq in APL as well as non-APL AML. APL showed a distinct chromatin profile that differed from non-APL AML.

Results

We describe APL-specific changes in H3K27ac, H3K9me3, and H3K27me3 with impact on enhancer activity, repression of transposable elements, and Polycomb regulated gene repression. The APL-specific H3K27ac pattern identifies APL-specific enhancer and super-enhancer regions, including a subset of enhancers that are bound by the PML-RARA fusion protein. While chromatin bound specifically by PML-RARA were dominantly active, APL was also characterized by gain of APL-specific heterochromatin states with significant gains of H3K9me3 enriched lamina-associated domains and the transposable elements LINE, LTR, and SINE.

Conclusion

These findings suggest a unique enhancer and heterochromatin profile in APL, with implications for transcription regulation and treatment response. These findings offer novel insights into the pathogenesis of APL.