ArticleBlood cancer discovery2020
Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia.
Article in Blood cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL.Science advances · 2025Article
- CABIN1 peptide effectively targets MEF2D-fusion protein in B-cell precursor acute lymphoblastic leukemia.Signal transduction and targeted therapy · 2025Article
- Molecular mechanisms of unique therapeutic potential of CUDC-907 for MEF2D fusion-driven BCP-ALL.Signal transduction and targeted therapy · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Acute lymphoblastic leukaemia.Nature reviews. Disease primers · 2024Review
- Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.Genome biology · 2024Article
- The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024Review
- BCL6 inhibition ameliorates resistance to ruxolitinib inHaematologica · 2023Article
- Oncogenic lesions and molecular subtypes in adults with B-cell acute lymphoblastic leukemia.Cancer science · 2023Review
- The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions.Bioengineering (Basel, Switzerland) · 2022Review
- Dissection of the MEF2D-IRF8 transcriptional circuit dependency in acute myeloid leukemia.iScience · 2022Article
- Linear and Circular Long Non-Coding RNAs in Acute Lymphoblastic Leukemia: From Pathogenesis to Classification and Treatment.International journal of molecular sciences · 2022Review
- Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines.Nature communications · 2022Article
- ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency.Molecular cell · 2021Article
- Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2021Review
- Core transcriptional regulatory circuitries in cancer.Oncogene · 2020Review
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27 authors at 10 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The cellular context that integrates gene expression, signaling, and metabolism dictates the oncogenic behavior and shapes the treatment responses in distinct cancer types. Although chimeric fusion proteins involving transcription factors (TF) are hallmarks of many types of acute lymphoblastic leukemia (ALL), therapeutically targeting the fusion proteins is a challenge. In this work, we characterize the core regulatory circuitry (CRC; interconnected autoregulatory loops of TFs) of B-ALL involving MEF2D-fusions and identify MEF2D-fusion and SREBF1 TFs as crucial CRC components. By gene silencing and pharmacologic perturbation, we reveal that the CRC integrates the pre-B-cell receptor (BCR) and lipid metabolism to maintain itself and govern malignant phenotypes. Small-molecule inhibitors of pre-BCR signaling and lipid biosynthesis disrupt the CRC and silence the MEF2D fusion in cell culture and show therapeutic efficacy in xenografted mice. Therefore, pharmacologic disruption of CRC presents a potential therapeutic strategy to target fusion protein-driven leukemia. SIGNIFICANCE: Cancer type-specific gene expression is governed by transcription factors involved in a highly interconnected autoregulatory loop called CRC. Here, we characterized fusion protein-driven CRC and identified its pharmacologic vulnerabilities, opening therapeutic avenues to indirectly target fusion-driven leukemia by disrupting its CRC.
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