ArticleOncogene2022
HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Cancer Prevalence Among Large Cohort of Individuals With Down Syndrome: Implications for Screening Guidelines.Cancer medicine · 2026Article
- A Link Between Allergy and Hematological Malignancies? Focus on Possible Mechanisms and the Potential Role of Biological Therapies.Clinical and translational allergy · 2026Review
- Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia.Cancer metastasis reviews · 2025Review
- B-Cell Acute Lymphoblastic Leukemia in a Child with Down Syndrome and High-Risk Genomic Lesions.Current issues in molecular biology · 2025Article
- Pan-cancer Multi-omics Analysis Reveals HMGN1 as a Potential Prognostic and Immune Infiltration-associated Biomarker.Current medicinal chemistry · 2025Article
- Thymic stromal lymphopoietin in leukemia: A double-edged sword?Leukemia research reports · 2025Review
- Efficacy of DYRK1A inhibitors in novel models of Down syndrome acute lymphoblastic leukemia.Haematologica · 2024Article
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
- Aberrant stem cell and developmental programs in pediatric leukemia.Frontiers in cell and developmental biology · 2024Review
- Article
- Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome.Biological research · 2023Article
- Down syndrome and leukemia: from basic mechanisms to clinical advances.Haematologica · 2023Review
- BCL6 inhibition ameliorates resistance to ruxolitinib inHaematologica · 2023Article
- Gain of chromosome 21 increases the propensity forFrontiers in oncology · 2023Article
- Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain.Epigenetics & chromatin · 2022Review
- FBXO42 facilitates Notch signaling activation and global chromatin relaxation by promoting K63-linked polyubiquitination of RBPJ.Science advances · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genetic basis of the predisposition for Down Syndrome (DS) patients to develop cytokine receptor-like factor 2 rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) is currently unknown. Genes located on chromosome 21 and expressed in hematopoietic cells are likely candidates for investigation of CRLF2r DS-ALL pathogenesis. We explored the high-mobility group nucleosome-binding protein 1 (HMGN1), located in the DS critical region, in an inducible CRISPR/Cas9 knockout (KO) xenograft model to assess the effect of HMGN1 loss of function on the leukemic burden. We demonstrated HMGN1 KO-mitigated leukemic phenotypes including hepatosplenomegaly, thrombocytopenia, and anemia, commonly observed in leukemia patients, and significantly increased survival in vivo. HMGN1 overexpression in murine stem cells and Ba/F3 cells in vitro, in combination with P2RY8-CRLF2, resulted in cytokine-independent transformation and upregulation of cell signaling pathways associated with leukemic development. Finally, in vitro screening demonstrated successful targeting of P2RY8-CRLF2 and HMGN1 co-expressing cell lines and patient samples with fedratinib (JAK2 inhibitor), and GSK-J4 (demethylase inhibitor) in combination. Together, these data provide critical insight into the development and persistence of CRLF2r DS-ALL and identify HMGN1 as a potential therapeutic target to improve outcomes and reduce toxicity in this high-risk cohort of young patients.
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