دورية أكاديمية

Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosisResearch in context

التفاصيل البيبلوغرافية
العنوان: Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosisResearch in context
المؤلفون: Jennine Grootens, Johanna S. Ungerstedt, Maria Ekoff, Elin Rönnberg, Monika Klimkowska, Rose-Marie Amini, Michel Arock, Stina Söderlund, Mattias Mattsson, Gunnar Nilsson, Joakim S. Dahlin
المصدر: EBioMedicine, Vol 43, Iss , Pp 150-158 (2019)
بيانات النشر: Elsevier, 2019.
سنة النشر: 2019
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Medicine, Medicine (General), R5-920
الوصف: Background: Systemic mastocytosis (SM) is a haematological disease characterised by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34+ haematopoietic progenitors can carry the mutation; however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single haematopoietic stem and progenitor cells. Methods: Fluorescence-activated single-cell index sorting and KIT D816V mutation assessment were applied to analyse mast cells and >10,000 CD34+ bone marrow progenitors across 10 haematopoietic progenitor subsets. In vitro assays verified cell-forming potential. Findings: We found that in SM 60–99% of the mast cells harboured the KIT D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the haematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the haematopoietic landscape of SM patients, from haematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that FcεRI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time. Interpretation: The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA. Keywords: Systemic Mastocytosis, Single-cell, Mast cell, Mast cell progenitor, CD45RA, Haematopoiesis, Haematopoietic stem cells, KIT D816V
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396419302348Test; https://doaj.org/toc/2352-3964Test
DOI: 10.1016/j.ebiom.2019.03.089
الوصول الحر: https://doaj.org/article/44d2448fcd544af3a5923d8153cdc1daTest
رقم الانضمام: edsdoj.44d2448fcd544af3a5923d8153cdc1da
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2019.03.089