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December 8, 2025BloodOpen Access

Somatic ASXL1 mutations in chronic myelomonocytic leukemia result in loss of imprinting control and overexpression of DLK1 through deregulation of DNA methylation

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Authors

CFChristy FinkeMPMrinal M. Patnaik

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Overview

Multiomic analyses reveal DNA methylation and loss of imprinting control contributes to DLK1 overexpression in chronic myelomonocytic leukemia.

Key Points

  • This research investigates the impact of ASXL1 mutations on DLK1 expression in chronic myelomonocytic leukemia (CMML).
  • Conducted multiomic analyses including bulk RNA-seq, ChIP-seq, and methylation profiling on CMML patient samples.
  • Analyzed histone modifications and differential gene expression between ASXL1 mutant and wild-type cases.
  • Performed digital droplet PCR to determine allelic status of DLK1 in ASXL1 mutant and wild-type cases.
  • Validated DLK1 overexpression in ASXL1 mutant cases compared to wild-type cases.
  • Identified global hypomethylation at the DLK1 regulatory regions in ASXL1 mutants.
  • Demonstrated a significant loss of imprinting control affecting DLK1 expression through methylation pattern analysis.

Cite This Study

Finke et al. (2025) studied this question.

synapsesocial.com/papers/69362f4b4fa91c937236d778https://doi.org/10.1182/blood-2025-1457
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