{"doi":"10.18632/oncotarget.28614","title":"Prevalence and impact of the <i>KIT</i> M541L variant in patients with mastocytosis","abstract":"// Luisa N. Dominguez Aldama 1 , * , Eric Karlins 3 , * , Xiaoping Sun 2 , Daniel Veltri 3 , Hirsh D. Komarow 1 , Irina Maric 2 , Dean D. Metcalfe 1 and Melody C. Carter 1 1 Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA 2 Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA 3 Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA * Co-first authorship Correspondence to: Melody C. Carter, email: mcarter@niaid.nih.gov Keywords: mastocytosis; KIT M541L; KIT D816V; adults; pediatrics Received: April 04, 2024&emsp;&emsp;&emsp;&emsp; Accepted: July 02, 2024&emsp;&emsp;&emsp;&emsp; Published: July 22, 2024 Copyright: &copy; 2024 Aldama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Activating mutations in KIT , particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis ( n = 100) compared to ancestry-matched 1000 genomes controls ( n = 500) and patients with idiopathic anaphylaxis ( n = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort ( n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the KIT M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.","journal":"Oncotarget","year":2024,"id":459831,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9657,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":448667,"name":"Eric Karlins","orcid":"0000-0002-7541-393X","position":1,"is_corresponding":false},{"id":445197,"name":"Xiaoping Sun","orcid":"0000-0002-7766-9306","position":2,"is_corresponding":false},{"id":299006,"name":"Daniel Veltri","orcid":"0000-0002-6101-6693","position":3,"is_corresponding":false},{"id":242063,"name":"Hirsh D. Komarow","orcid":"0000-0001-7012-9406","position":4,"is_corresponding":false},{"id":280055,"name":"Irina Marić","orcid":null,"position":5,"is_corresponding":false},{"id":242067,"name":"Dean D. Metcalfe","orcid":"0000-0002-7781-8260","position":6,"is_corresponding":false},{"id":242065,"name":"Melody C. Carter","orcid":"0000-0003-0379-5366","position":7,"is_corresponding":false},{"id":969120,"name":"Luisa N. Dominguez Aldama","orcid":null,"position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:03:59.428859Z","pmid":"39037378","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}