SynthesisBlood2019
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome.
Synthesis in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed, 65 citations in OpenAlex.
- Promoting Research Excellence in Down Syndrome: Proceedings of the 5th International Conference of the Trisomy 21 Research Society.Neuromolecular medicine · 2026Article
- Epidemiological trends and burden projections of childhood leukemia in China: age-stratified analysis and impact of COVID-19 from 1990 to 2035.Annals of hematology · 2026Article
- Phthalates measured at birth and risk of testicular cancer in adolescents and young adults.JNCI cancer spectrum · 2026Article
- The very rare association between T-cell acute lymphoblastic leukemia and down syndrome: a case report and review of the literature.Frontiers in pediatrics · 2026Article
- Long-term trends in the burden of leukemia subtypes in China from 1990 to 2021: a Joinpoint regression and age-period-cohort analysis based on GBD 2021.Frontiers in medicine · 2026Article
- Article
- The Unique Utility of Newborn Dried Blood Spots for Driving Discovery in Childhood Cancer Research.Clinical chemistry · 2025Review
- A multicenter observational cohort study in survivors of Down Syndrome-associated acute leukemia (ALTE22C1): a report from the Children's Oncology Group.BMC cancer · 2025Observational
- The global, regional, and national burden of acute lymphoblastic leukemia, 1990 to 2021: a cross-sectional analysis from the 2021 global burden of disease study.Discover oncology · 2025Article
- Genome-wide association study of somatic GATA1s mutations in newborns with Down syndrome.Blood advances · 2025Article
- The Interrelationship between Preconception Folate Nutritional Intake and Child Genetic Liability in the Risk of Childhood Acute Lymphoblastic Leukemia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- Review
- Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024Review
- Concepts in B cell acute lymphoblastic leukemia pathogenesis.Journal of leukocyte biology · 2024Review
- Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex.American journal of medical genetics. Part A · 2024Article
- A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.Cell genomics · 2024Article
- Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.International journal of cancer · 2024Article
- Down syndrome-associated leukaemias: current evidence and challenges.Therapeutic advances in hematology · 2024Review
- Advancing Diagnostics and Therapy to Reach Universal Cure in Childhood ALL.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- Article
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Authors and funding
48 authors at 20 institutions in 4 countries.
Funding
Abstract
Children with Down syndrome (DS) have a 20-fold increased risk of acute lymphoblastic leukemia (ALL) and distinct somatic features, including CRLF2 rearrangement in ∼50% of cases; however, the role of inherited genetic variation in DS-ALL susceptibility is unknown. We report the first genome-wide association study of DS-ALL, comprising a meta-analysis of 4 independent studies, with 542 DS-ALL cases and 1192 DS controls. We identified 4 susceptibility loci at genome-wide significance: rs58923657 near IKZF1 (odds ratio [OR], 2.02; Pmeta = 5.32 × 10-15), rs3731249 in CDKN2A (OR, 3.63; Pmeta = 3.91 × 10-10), rs7090445 in ARID5B (OR, 1.60; Pmeta = 8.44 × 10-9), and rs3781093 in GATA3 (OR, 1.73; Pmeta = 2.89 × 10-8). We performed DS-ALL vs non-DS ALL case-case analyses, comparing risk allele frequencies at these and other established susceptibility loci (BMI1, PIP4K2A, and CEBPE) and found significant association with DS status for CDKN2A (OR, 1.58; Pmeta = 4.1 × 10-4). This association was maintained in separate regression models, both adjusting for and stratifying on CRLF2 overexpression and other molecular subgroups, indicating an increased penetrance of CDKN2A risk alleles in children with DS. Finally, we investigated functional significance of the IKZF1 risk locus, and demonstrated mapping to a B-cell super-enhancer, and risk allele association with decreased enhancer activity and differential protein binding. IKZF1 knockdown resulted in significantly higher proliferation in DS than non-DS lymphoblastoid cell lines. Our findings demonstrate a higher penetrance of the CDKN2A risk locus in DS and serve as a basis for further biological insights into DS-ALL etiology.
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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.