ArticleHaematologica2016
Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00001163 (Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.International journal of molecular sciences · 2025Review
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- Article
- Germline predisposition to myeloid neoplasms: Characteristics and management of high versus variable penetrance disorders.Best practice & research. Clinical haematology · 2024Review
- Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome.International journal of molecular sciences · 2024Review
- Sporadic and Familial Acute Myeloid Leukemia with CEBPA Mutations.Current hematologic malignancy reports · 2023Review
- Current Landscape of Genome-Wide Association Studies in Acute Myeloid Leukemia: A Review.Cancers · 2023Review
- Hereditary acute myeloid leukemia associated with C-terminal CEBPA germline variants.Familial cancer · 2023Review
- Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies-A Review.Cancers · 2022Review
- Article
- Advances in germline predisposition to acute leukaemias and myeloid neoplasms.Nature reviews. Cancer · 2021Review
- [Investigation and clinical analysis of a family with germline CEBPA mutations in acute myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Article
- Companion gene mutations and their clinical significance in AML with double mutant CEBPA.Cancer gene therapy · 2020Article
- Secondary leukemia in patients with germline transcription factor mutations (RUNX1, GATA2, CEBPA).Blood · 2020Review
- Genetic Predisposition to Myelodysplastic Syndrome in Clinical Practice.Hematology/oncology clinics of North America · 2020Review
- The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.Nature communications · 2020Article
- Transcription factor mutations as a cause of familial myeloid neoplasms.The Journal of clinical investigation · 2019Review
- Genomic approaches to accelerate cancer interception.The Lancet. Oncology · 2017Review
- Index case of acute myeloid leukemia in a family harboring a novelBlood advances · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.
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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.