ArticleThe Journal of clinical investigation2021
Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children.Blood · 2024Trial
- Preemptive hematopoietic stem cell transplantation inHaematologica · 2026Article
- Cytogenetic and Molecular Analysis of a "Double-Hit" RUNX1 Including a RUNX1 p.Trp279* and a Cryptic Novel t(6;21)(q25;q22)/RUNX1::ARID1B in Acute Myeloid Leukemia.Genes, chromosomes & cancer · 2026Article
- The splicing factor PTBP1 interacts with RUNX1 and is required for leukemia cell survival.Leukemia · 2026Article
- Review
- An Account of Acute Myeloid Leukemia Complicating Pregnancy and Literature Review.Diagnostics (Basel, Switzerland) · 2025Article
- The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia.Nature communications · 2025Article
- Hereditary Hematopoietic Malignancies: Considerations for Optimizing Diagnosis and Management.Current oncology reports · 2025Review
- Closing the loop: Teaching single-cell foundation models to learn from perturbations.bioRxiv : the preprint server for biology · 2025Article
- Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo.Leukemia · 2025Article
- scNucMap: mapping the nucleosome landscapes at single-cell resolution.Bioinformatics (Oxford, England) · 2025Article
- Review
- Genetic predisposition to myelodysplastic syndrome: Genetic counseling and transplant implications.Seminars in hematology · 2024Review
- Leukemia in pregnancy: Diagnosis and therapeutic approach (Review).Molecular and clinical oncology · 2024Review
- Acute lymphoblastic leukaemia.Nature reviews. Disease primers · 2024Review
- Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy.Blood advances · 2024Article
- Article
- Identification of TCF3 germline variants in pediatric B-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26.Blood · 2023Article
- GermlineEJHaem · 2023Article
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Authors and funding
27 authors at 11 institutions in 3 countries.
Funding
Abstract
Genetic alterations in the RUNX1 gene are associated with benign and malignant blood disorders, particularly of megakaryocyte and myeloid lineages. The role of RUNX1 in acute lymphoblastic leukemia (ALL) is less clear, particularly how germline genetic variation influences the predisposition to this type of leukemia. Sequencing 4,836 children with B-ALL and 1,354 cases of T-ALL, we identified 31 and 18 germline RUNX1 variants, respectively. RUNX1 variants in B-ALL consistently showed minimal damaging effects. By contrast, 6 T-ALL-related variants result in drastic loss of RUNX1 activity as a transcription activator in vitro. Ectopic expression of dominant-negative RUNX1 variants in human CD34+ cells repressed differentiation into erythroid, megakaryocytes, and T cells, while promoting myeloid cell development. Chromatin immunoprecipitation sequencing of T-ALL models showed distinctive patterns of RUNX1 binding by variant proteins. Further whole genome sequencing identified JAK3 mutation as the most frequent somatic genomic abnormality in T-ALL with germline RUNX1 variants. Co-introduction of RUNX1 variant and JAK3 mutation in hematopoietic stem and progenitor cells in mice gave rise to T-ALL with early T-cell precursor phenotype. Taken together, these results indicated that RUNX1 is an important predisposition gene for T-ALL and pointed to novel biology of RUNX1-mediated leukemogenesis in the lymphoid lineages.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.