{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T14:46:02Z","timestamp":1775227562835,"version":"3.50.1"},"reference-count":55,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Here, we show that plasma metabolomic profiles were able to discriminate indolent from advanced forms of the disease. We identified N-acetyl-d-glucosamine (GlcNAc) as the most predictive metabolite of SM severity. High plasma levels of GlcNAc in patients with advanced SM correlated with the activation of the GlcNAc-fed hexosamine biosynthesis pathway in patients BM aspirates and purified BM MCs. At the functional level, GlcNAc enhanced human neoplastic MCs proliferation and promoted rapid health deterioration in a humanized mouse model of SM. In addition, in the presence of GlcNAc, immunoglobulin E-stimulated MCs triggered enhanced release of proinflammatory cytokines and a stronger acute response in a mouse model of passive cutaneous anaphylaxis. Mechanistically, elevated GlcNAc levels promoted the transcriptional accessibility of chromatin regions that contain genes encoding mediators of receptor tyrosine kinases cascades and inflammatory responses, thus leading to a more aggressive phenotype. Therefore, GlcNAc is an oncometabolite driver of SM aggressiveness. This study suggests the therapeutic potential for targeting metabolic pathways in MC-related diseases to manipulate MCs effector functions.<\/jats:p>","DOI":"10.1182\/blood.2020008948","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T16:41:30Z","timestamp":1620751290000},"page":"1590-1602","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":5,"title":["GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness"],"prefix":"10.1182","volume":"138","author":[{"given":"Julie","family":"Agopian","sequence":"first","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"},{"name":"French Reference Center for Mastocytosis (CEREMAST), Paris, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8904-9131","authenticated-orcid":false,"given":"Quentin","family":"Da Costa","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quang Vo","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Scorrano","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paraskevi","family":"Kousteridou","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yuan","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabie","family":"Chelbi","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"},{"name":"Inovarion, Paris, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7332-1337","authenticated-orcid":false,"given":"Armelle","family":"Goubard","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remy","family":"Castellano","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-5125","authenticated-orcid":false,"given":"Julien","family":"Maurizio","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy (CIML), INSERM U631, CNRS UMR 6102, Aix-Marseille Universit\u00e9, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-7199","authenticated-orcid":false,"given":"Cristina","family":"Teodosio","sequence":"additional","affiliation":[{"name":"Department of Immunohematology, Leiden University Medical Center, ZC Leiden, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8295-5414","authenticated-orcid":false,"given":"Paulo","family":"De Sepulveda","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-2589","authenticated-orcid":false,"given":"John M.","family":"Asara","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), University of Salamanca, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain;"},{"name":"Spanish Network on Mastocytosis (REMA), Toledo, Spain; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2574-3874","authenticated-orcid":false,"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[{"name":"French Reference Center for Mastocytosis (CEREMAST), Paris, France;"},{"name":"Institut Imagine, INSERM U1163, CNRS Equipe de Recherche Labelis\u00e9e (ERL) 8654, Paris Universit\u00e9, Service d\u2019H\u00e9matologie Clinique, H\u00f4pital Necker-Enfants Malades, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-1150","authenticated-orcid":false,"given":"Patrice","family":"Dubreuil","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"},{"name":"French Reference Center for Mastocytosis (CEREMAST), Paris, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-1096","authenticated-orcid":false,"given":"Fabienne","family":"Brenet","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), INSERM U1068, Unit\u00e9 Mixte de Recherche (UMR) 258 Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Universit\u00e9, Institut Paoli-Calmettes, Equipe Labellis\u00e9e Ligue Contre le Cancer, Marseille, France;"},{"name":"French Reference Center for Mastocytosis (CEREMAST), Paris, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"issue":"4","key":"2021102815242455300_B1","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1182\/blood-2007-11-078097","article-title":"Mast cells and 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