{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:21:22Z","timestamp":1783606882669,"version":"3.55.0"},"reference-count":123,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Systemic mastocytosis (SM) was historically classified as a myeloproliferative neoplasm, but it was redefined in 2016 as a distinct entity in the World Health Organization classification. Characterized by abnormal mast cell (MC) proliferation, SM can present as a cutaneous form or as a systemic disease involving multiple organs. It spans a spectrum from indolent forms with an excellent prognosis to more aggressive variants associated with organ dysfunction and life\u2010threatening complications. The most significant molecular discovery in SM is the presence of mutations in the <jats:italic>KIT<\/jats:italic> gene, particularly D816V, which plays a pivotal role in disease progression. Additional mutations in genes such as <jats:italic>SRSF2<\/jats:italic>, <jats:italic>ASXL1<\/jats:italic>, and <jats:italic>TET2<\/jats:italic> have been identified, contributing to the genetic complexity of SM and influencing clinical outcomes. The bone marrow microenvironment plays a critical role in the pathogenesis of SM, serving as the primary site for MC proliferation and influencing disease progression through interactions with various cellular components. This review highlights the importance of the bone marrow microenvironment in sustaining abnormal MC proliferation and activation, providing insights into potential therapeutic strategies targeting these interactions. We also explore the genetic and molecular mechanisms involved, underscoring their diagnostic and therapeutic implications.<\/jats:p>","DOI":"10.1111\/ejh.70004","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T23:40:03Z","timestamp":1751326803000},"page":"308-321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathogenic Mechanisms of Systemic Mastocytosis: Unraveling the Genetic Complexity, Bone Marrow Microenvironment, and Clinical Challenges"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2051-9267","authenticated-orcid":false,"given":"Christina D.","family":"Sotiropoulou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Festas","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, National and Kapodistrian University of Athens, School of Medicine Attikon University Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9935-8461","authenticated-orcid":false,"given":"Christos K.","family":"Kontos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Makris","sequence":"additional","affiliation":[{"name":"Allergy Unit \u201cD. Kalogeromitros\u201d, 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, School of Medicine University General Hospital \u201cAttikon\u201d  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis G.","family":"Foukas","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, National and Kapodistrian University of Athens, School of Medicine Attikon University Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3376-837X","authenticated-orcid":false,"given":"Sotirios G.","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine and Research Unit, Hematology Unit, National and Kapodistrian University of Athens, School of Medicine University General Hospital \u201cAttikon\u201d  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15235626"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-022-03423-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2011.09.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002496"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-024-00737-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18116"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14102487"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2015.1.98"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-686626"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-019-08769-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.08.044"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2023.194912"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043090"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.37"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19501"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13865"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.14740\/jmc3552"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16126"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21005-w"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-23-0195"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062964"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.190"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-02094-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2021.1941925"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.07.012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.04.006"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-23-0115"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010411"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002889"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2020.106404"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003980"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062983"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000932"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2010.35"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35559"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1427563"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1443704"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16092"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2023.107345"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12206429"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2177"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006242"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100693"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2008.01942.x"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12601"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000305552"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000059404"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2022.040"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2021.1959315"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19245"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0222"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2022.073"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406207231205643"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-023-01123-9"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014612"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.7134"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1177\/10781552231221149"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.002"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14800"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3MR0117-033R"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2024.06.005"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12607"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2004.12.004"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13231"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158772"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728214.2023.2221028"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10071420"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.06.021"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000621"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011270"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2010.03685.x"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.794974"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8619-2"},{"key":"e_1_2_11_76_1","first-page":"683","article-title":"Role and Significance of c\u2010KIT Receptor Tyrosine Kinase in Cancer: A Review","volume":"22","author":"Sheikh E.","year":"2022","journal-title":"Bosnian Journal of Basic Medical Sciences"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.012"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.04.017"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01493-2"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.07.009"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.234864"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214004"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.01.033"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084462"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32228-w"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310679"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891268"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054811"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01494-1"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06188-0"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2025.111334"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095208"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00163"},{"issue":"11","key":"e_1_2_11_94_1","article-title":"Osteoporosis in Systemic Mastocytosis: A Scoping Review","volume":"60","author":"Letizia Mauro G.","year":"2024","journal-title":"Medicina (Kaunas, Lithuania)"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01394-2"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.088"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030481"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463201302600206"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2005.01.011"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.176"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13217"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020515"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.53"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6604"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_14"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.05.028"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14734"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122900"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S366367"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1111\/vcp.13098"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0260-3"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04393-z"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2011.09.007"},{"key":"e_1_2_11_114_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1098129"},{"key":"e_1_2_11_115_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-22-0595"},{"key":"e_1_2_11_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109695"},{"key":"e_1_2_11_117_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00788"},{"key":"e_1_2_11_118_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00045.2017"},{"key":"e_1_2_11_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00742-y"},{"key":"e_1_2_11_120_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147703"},{"key":"e_1_2_11_121_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.964442"},{"key":"e_1_2_11_122_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines4030028"},{"key":"e_1_2_11_123_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1129343"},{"key":"e_1_2_11_124_1","first-page":"699","article-title":"Allogeneic Haematopoietic Cell Transplantation for Advanced Systemic Mastocytosis: Best Practice Recommendations on Behalf of the EBMT Practice Harmonisation and Guidelines Committee","volume":"38","author":"McLornan D. P.","year":"2024","journal-title":"Leukemia"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.70004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T07:51:57Z","timestamp":1756799517000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.70004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":123,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/ejh.70004"],"URL":"https:\/\/doi.org\/10.1111\/ejh.70004","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"assertion":[{"value":"2025-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}