Trial reportHuman genetics2015
Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family.
Trial report in Human genetics, 2015. 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 16 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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 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
- Disruption of CTCF binding by germline non-coding variants inmedRxiv : the preprint server for health sciences · 2026Article
- Review
- Immunological and hematological findings as major features in a patient with a new germline pathogenic CBL variant.American journal of medical genetics. Part A · 2024Article
- Chronic myeloproliferative neoplasm in adulthood in CBL syndrome harboring a splice-siteEJHaem · 2024Article
- Long non-coding RNA small nucleolar RNA host gene 29 drives chronic myeloid leukemia progression via microRNA-483-3p/Casitas B-lineage Lymphoma axis-mediated activation of the phosphoinositide 3-kinase/Akt pathway.Medical oncology (Northwood, London, England) · 2024Article
- Clinical and molecular features ofHaematologica · 2023Article
- Integrated Analysis of Coexpression and Exome Sequencing to Prioritize Susceptibility Genes for Familial Cutaneous Melanoma.The Journal of investigative dermatology · 2022Article
- Review
- Somatic variation as an incidental finding in the pediatric next-generation sequencing era.Cold Spring Harbor molecular case studies · 2021Article
- Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice-site mutations: Two case reports and a literature review.Clinical case reports · 2021Article
- Cracking the Monoubiquitin Code of Genetic Diseases.International journal of molecular sciences · 2020Review
- Rare germline variants in known melanoma susceptibility genes in familial melanoma.Human molecular genetics · 2017Article
- Unexpected Findings in a Child with Atypical Hemolytic Uremic Syndrome: An Example of How Genomics Is Changing the Clinical Diagnostic Paradigm.Frontiers in pediatrics · 2017Article
- Research participant interest in primary, secondary, and incidental genomic findings.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Article
- VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease.Oncotarget · 2016Article
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 2 institutions in 1 country.
Funding
Abstract
Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative neoplasm that arises from malignant transformation of the stem cell compartment and results in increased production of myeloid cells. Somatic and germline variants in CBL (Casitas B-lineage lymphoma proto-oncogene) have been associated with JMML. We report an incompletely penetrant CBL Y371C mutation discovered by whole-exome sequencing in three individuals with JMML in a large pedigree with 35 years of follow-up. The Y371 residue is highly evolutionarily conserved among CBL orthologs and paralogs. In silico bioinformatics prediction programs suggested that the Y371C mutation is highly deleterious. Protein structural modeling revealed that the Y371C mutation abrogated the ability of the CBL protein to adopt a conformation that is required for ubiquitination. Clinically, the three mutation-positive JMML individuals exhibited variable clinical courses; in two out of three, primary hematologic abnormalities persisted into adulthood with minimal clinical symptoms. The penetrance of the CBL Y371C mutation was 30% for JMML and 40% for all leukemia. Of the 8 mutation carriers in the family with available photographs, only one had significant dysmorphic features; we found no evidence of a clinical phenotype consistent with a "CBL syndrome". Although CBL Y371C has been previously reported in familial JMML, we are the first group to follow a complete pedigree harboring this mutation for an extended period, revealing additional information about this variant's penetrance, function and natural history.
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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.