Trial reportBlood2022
Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.
Trial report in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed.
- Decreased TXNRD1 is associated with resistance to tagraxofusp in blastic plasmacytoid dendritic cell neoplasms, as seen in phase II.Leukemia · 2026Trial
- A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD.Annals of hematology · 2025Trial
- Preemptive hematopoietic stem cell transplantation inHaematologica · 2026Article
- Article
- Hair bulb and oral mucosa DNA for prompt germline testing in hematologic neoplasms.Blood cancer journal · 2026Article
- Performance and clinical utility of Spanish germ line genetic testing criteria for hematologic neoplasms predisposition.Blood advances · 2026Article
- Cancer risk in adults with pathogenic germline variants in RAS/MAPK genes using genomic ascertainment.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Elevated Allele Frequency of a Common GermlineCancers · 2026Article
- Impact of Germline CHEK2 Pathogenic Variants on the Risk of Acute Myeloid Leukemia and Myelodysplastic Syndrome.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Refinement of the classification of DDX41 variants through analysis of aggregated clinical datasets.Leukemia · 2026Article
- Serial next-generation sequencing for detecting germline predisposition in acute myeloid leukemia.Haematologica · 2026Article
- Beyond somatic mutations: the role of next-generation sequencing in identifying germline predisposition in patients with acute myeloid leukemia.Haematologica · 2026Article
- Impact of Germline DNA Repair Mutations on Clonal Hematopoiesis and Myeloid Neoplasm Development.Current hematologic malignancy reports · 2025Review
- Noonan Syndrome, Cancer Risk, and Growth Hormone TreatmentJournal of clinical research in pediatric endocrinology · 2025Review
- Spliceosomal GTPase EFTUD2 mediates DDX41 intron retention to promote the malignant progression of ovarian cancer.British journal of cancer · 2025Article
- Implementing a Genetic Counselor-Led Model for Hereditary Myeloid Malignancies: A Real-World Study.Cancer medicine · 2025Article
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Validation of Guidelines for Genetic Investigation of Myeloid Neoplasms with Germline Predisposition: Results from a Prospective Cohort Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Inherited predisposition to myeloid malignancies is more common than previously appreciated. We analyzed the whole-exome sequencing data of paired leukemia and skin biopsy samples from 391 adult patients from the Beat AML 1.0 consortium. Using the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines for variant interpretation, we curated 1547 unique variants from 228 genes. The pathogenic/likely pathogenic (P/LP) germline variants were identified in 53 acute myeloid leukemia (AML) patients (13.6%) in 34 genes, including 6.39% (25/391) of patients harboring P/LP variants in genes considered clinically actionable (tier 1). 41.5% of the 53 patients with P/LP variants were in genes associated with the DNA damage response. The most frequently mutated genes were CHEK2 (8 patients) and DDX41 (7 patients). Pathogenic germline variants were also found in new candidate genes (DNAH5, DNAH9, DNMT3A, and SUZ12). No strong correlation was found between the germline mutational rate and age of AML onset. Among 49 patients who have a reported history of at least one family member affected with hematological malignancies, 6 patients harbored known P/LP germline variants and the remaining patients had at least one variant of uncertain significance, suggesting a need for further functional validation studies. Using CHEK2 as an example, we show that three-dimensional protein modeling can be one of the effective methodologies to prioritize variants of unknown significance for functional studies. Further, we evaluated an in silico approach that applies ACMG curation in an automated manner using the tool for assessment and (TAPES) prioritization in exome studies, which can minimize manual curation time for variants. Overall, our findings suggest a need to comprehensively understand the predisposition potential of many germline variants in order to enable closer monitoring for disease management and treatment interventions for affected patients and families.
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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 Socratic graph.