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December 8, 2025Blood

SETD2 deficiency in chronic myeloid leukemia (CML) contributes to tyrosine kinase inhibitor (TKI) resistance and disease acceleration by enhancing genetic instability and rewiring cellular metabolism and might be a novel biomarker of high risk disease since diagnosis

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Authors

LRLucia RomagnoliAOAndrea OldaniAMAlessandra Merlotti

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Overview

Analysis uncovers SETD2 LOF contributes to TKI resistance and metabolic rewiring in chronic myeloid leukemia, suggesting its potential as a biomarker.

Key Points

  • To investigate the role of SETD2 loss-of-function in chronic myeloid leukemia and its implications for TKI resistance and disease progression.
  • Analyzed primary CD34+ progenitors and CML cellular models with SETD2 silenced or overexpressed.
  • Utilized techniques including chromatin immunoprecipitation sequencing and immunofluorescence.
  • Conducted differential transcriptomic profiling and interactome analysis using mass spectrometry.
  • SETD2 deficiency enhances leukemic cell proliferation by more than 50%.
  • SETD2 LOF leads to transcriptional regulation of genes associated with DNA repair and metabolism.
  • SETD2 can be detected in total leukocytes, serving as a biomarker for high-risk disease.

Cite This Study

Romagnoli et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d3edhttps://doi.org/10.1182/blood-2025-5557
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Novel roles of SETD2 in tumor metabolism and immunotherapy: a systematic review and meta-analysis2026
  2. 2SETD2 Deficiency Drives Mitochondrial DNA Leakage and Creates a Druggable Dependency on BCL-XL in Clear Cell Renal Cell Carcinoma.2026
  3. 3The SETD2 L1609P mutation found in leukemia disrupts methyltransferase activity and reduces histone H3K36 trimethylation2026
  4. 4Abstract 3194: <i>SETD4</i> regulates cell proliferation and methotrexate response in pediatric acute lymphoblastic leukemia2026
  5. 5Pharmacologic and Oncohistone Inhibition of SETD2 Converge on Genomic Instability2026 · 1 citations