ArticleBlood2023
RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- DLK1 is a GATA1s-driven dependency and therapeutic target in Down syndrome-associated myeloid leukemia.Blood advances · 2026Article
- Cancer Prevalence Among Large Cohort of Individuals With Down Syndrome: Implications for Screening Guidelines.Cancer medicine · 2026Article
- Exercise Attenuates Aortic Dissection Via PDE5A-Mediated Inhibition of Vascular Smooth Muscle Cell Phenotypic Switch.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Single cell transcriptional evolution of myeloid leukemia of Down syndrome.Nature communications · 2026Article
- Targeting RUNX1 Germline Variants: Agents Under Investigation.Current hematologic malignancy reports · 2025Review
- The Dual Role of RUNX1 in Inflammation-Driven Age-Related Diseases: From Molecular Mechanisms to Clinical Translation.Biomedicines · 2025Review
- Discovery of the U2AF1-UHM Inhibitor That Possesses Anti-Leukemia Activity In Vitro.ACS medicinal chemistry letters · 2025Article
- Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia.Cancer metastasis reviews · 2025Review
- An Isoform-Specific RUNX1C-BTG2 Axis Governs AML Quiescence and Chemoresistance.Blood cancer discovery · 2025Article
- RUNX1A isoform is overexpressed in acute myeloid leukemia and is associated with FLT3 internal tandem duplications.Cancer gene therapy · 2025Article
- Genome-wide association study of somatic GATA1s mutations in newborns with Down syndrome.Blood advances · 2025Article
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- DYRK1A in blood and immune function: implications in leukemia, inflammatory disorders, infection and Down syndrome.Frontiers in cell and developmental biology · 2025Review
- Article
- RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.Journal of thrombosis and haemostasis : JTH · 2024Article
- Cancer, metastasis, and the epigenome.Molecular cancer · 2024Review
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
- RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Commented on by
Authors and funding
25 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications of Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk of leukemia development. Here, we propose that RUNX1 isoform disequilibrium with RUNX1A bias is key to DS-associated myeloid leukemia (ML-DS). Starting with Hsa21-focused CRISPR-CRISPR-associated protein 9 screens, we uncovered a strong and specific RUNX1 dependency in ML-DS cells. Expression of the RUNX1A isoform is elevated in patients with ML-DS, and mechanistic studies using murine ML-DS models and patient-derived xenografts revealed that excess RUNX1A synergizes with the pathognomonic Gata1s mutation during leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium in patient-derived xenografts in vitro and in vivo. Moreover, pharmacological interference with MYC:MAX dimerization using MYCi361 exerted strong antileukemic effects. Thus, our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidy, and paves the way for the development of specific and targeted therapies for ML-DS, as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.