Evidence map›Paper›PMID 40789457›Full record

ArticleThe Journal of allergy and clinical immunology2025

Well-differentiated systemic mastocytosis: Genetics, mast cell immunophenotypes, and KIT autophosphorylation.

Brandon J Schornack, Jeremy C McMurray, Maria Leondaridis, Xiaoping Sun, Jeffrey R Stinson, Amaya James, Janet A Brunader, Kip R Hartman, Joaquin Villar, Clifton L Dalgard and 12 more

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In one paragraph

Article in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from 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.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

22 authors.

Brandon J SchornackAllergy, Immunology, & Immunizations Service, Walter Reed National Military Medical Center, Bethesda, Md; Department of Pediatrics, Uniformed Services University, Bethesda, Md.
Jeremy C McMurrayAllergy, Immunology, & Immunizations Service, Walter Reed National Military Medical Center, Bethesda, Md; Department of Pediatrics, Uniformed Services University, Bethesda, Md.
Maria LeondaridisDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda, Md.
Xiaoping SunHematology Section, Department of Laboratory Medicine, National Institutes of Health (NIH), Bethesda, Md.
Jeffrey R StinsonHematology Section, Department of Laboratory Medicine, National Institutes of Health (NIH), Bethesda, Md; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Md.
Amaya JamesHematology Section, Department of Laboratory Medicine, National Institutes of Health (NIH), Bethesda, Md; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Md.
Janet A BrunaderImmunization Healthcare Division, Defense Health Agency, Falls Church, Va.
Kip R HartmanPediatric Hematology Oncology Service, Walter Reed National Military Medical Center, Bethesda, Md.
Joaquin VillarHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Md; Center for Military Precision Health, Uniformed Services University, Bethesda, Md.
Clifton L DalgardDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University, Bethesda, Md; The American Genome Center, Uniformed Services University, Bethesda, Md.
Lydia D HellwigCenter for Military Precision Health, Uniformed Services University, Bethesda, Md; Department of Pediatrics, Uniformed Services University, Bethesda, Md.
Aubrey N MontebelloDepartment of Dermatology, Walter Reed National Military Medical Center, Bethesda, Md.
Pinar Engin ZerkLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Anna L GuarnieriCogent Biosciences Inc, Waltham, Mass.
Yeyun ZhouCogent Biosciences Inc, Waltham, Mass.
Ravi K JalluriCogent Biosciences Inc, Waltham, Mass.
Eric M PryorHematopathology Service, Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Md.
Andrew L SnowDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda, Md.
Tracy I GeorgeDepartment of Pathology, ARUP Laboratories and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
Melody C CarterMast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md.
Irina MaricHematology Section, Department of Laboratory Medicine, National Institutes of Health (NIH), Bethesda, Md.
Nathan A BoggsAllergy, Immunology, & Immunizations Service, Walter Reed National Military Medical Center, Bethesda, Md; Department of Medicine, Uniformed Services University, Bethesda, Md. Electronic address: nathan.boggs@usuhs.edu.

Funding

The Natural History of Pediatric Onset Cutaneous and Systemic MastocytosisZIAAI001127 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CARTER, MELODY C · 2010 to 2012
$600k
Intramural NIH HHS ZIA AI001127
6 · The paper itself

Abstract

backgroundWell-differentiated systemic mastocytosis (WDSM) is a rare myeloid neoplasm where the genetic etiology is often unknown.

objectiveWe aimed to assess WDSM patients for novel KIT variants, mast cell (MC) aberrant immunophenotypes, and KIT autophosphorylation patterns.

methodsNext-generation sequencing, MC immunophenotyping, and KIT autophosphorylation studies were performed.

resultsAmong 454 SM patients, there were 432 with KIT p.D816V+ SM and 4 with KIT p.D816Y+ SM-notably, none of these patients had WDSM. Of the remaining patients, we identified 7 with WDSM (1.5%) and 2 relatives with mastocytosis in skin. Next-generation sequencing revealed that 6 of 9 subjects carried known or novel germline KIT variants corresponding to regions outside of codon 816. Three patients had germline KIT p.K509I; 2 had germline KIT p.A533D; 1 had two germline KIT variants p.F681L and p.M541L; and 3 had no KIT mutation. Intracellular expression of CD2 and CD25 and less robust expression of CD30 was observed in MCs from WDSM patients. By developing a novel transient transfection assay in 293T cells, we found that unlike KIT p.D816F/V/Y variants that exhibit nearly exclusive intracellular localization and strong ligand-independent autophosphorylation (class II), WDSM-associated KIT variants showed enhanced ligand-dependent autophosphorylation relative to wild type (class I).

conclusionsOur study doubles the number of KIT variants identified in WDSM patients. No KIT p.D816V+ SM patient had WDSM. Intracellular CD2 and CD25 expression was more robustly detected in MCs from WDSM patients compared to CD30.

Indexed as

Mast CellsMastocytosis, SystemicProto-Oncogene Proteins c-kitAdultAgedCD2 AntigensFemaleHumansImmunophenotypingInterleukin-2 Receptor alpha SubunitMaleMiddle AgedYoung AdultCD2 AntigensIL2RA protein, humanInterleukin-2 Receptor alpha SubunitKIT protein, humanProto-Oncogene Proteins c-kitclass I KIT variantsKIT autophosphorylationmast cell immunophenotypesnext-generation sequencingWell-differentiated systemic mastocytosis

Identifiers

PMID40789457
PMCPMC12525888

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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 OpenQuestion graph.