{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:00:03Z","timestamp":1788368403084,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Myeloid sarcoma (MS) is a mass\u2010forming extramedullary manifestation of myeloid blasts, either in relation to an underlying acute myeloid leukemia (AML), another myeloid neoplasm (MN) or as a\n                    <jats:italic>de novo<\/jats:italic>\n                    occurrence. Data on the genetic profile of MS are sparse. In this study, 41 MS of 34 patients, including 7\n                    <jats:italic>de novo<\/jats:italic>\n                    cases and 24 patients with antecedent or synchronous MN, were analyzed with targeted next\u2010generation sequencing (NGS), RNA\u2010based fusion detection, and gene expression profiling (GEP). In 10 patients, a MS developed after stem cell transplantation for MN. Additionally, 21 available pre\u2010transplant bone marrow biopsies (BMB) from 20 patients and 6 post\u2010transplant BMB from 6 patients were investigated. The most frequently mutated gene was\n                    <jats:italic>TET2<\/jats:italic>\n                    (41%), followed by\n                    <jats:italic>NPM1<\/jats:italic>\n                    (38%) and\n                    <jats:italic>NRAS<\/jats:italic>\n                    (35%). Overall, 74% of the cases exhibited mutations affecting the MAPK\/ERK pathway. AML\u2010type fusions were detected in seven MS patients, who were younger than those without fusions (median 49 versus 67\u2009years). Nine of 13 patients with a MN and available pre\u2010transplant BMB showed additional mutations restricted to the MS, including an additional\n                    <jats:italic>NRAS<\/jats:italic>\n                    mutation in 3\/5 cases with AML. Five of seven of patients with pre\u2010transplant BMB without evidence of a MN revealed clonal hematopoiesis (CH), mostly shared\n                    <jats:italic>TET2<\/jats:italic>\n                    mutations. Comparative GEP between BM and MS revealed upregulation of the MAPK\/ERK pathway in MS and of gene sets relevant for interaction with the microenvironment. In conclusion, MS is characterized by a high incidence of\n                    <jats:italic>MAPK\/ERK<\/jats:italic>\n                    pathway mutations and activation, frequent clonal evolution, and association with CH in elderly patients without recurrent AML\u2010type fusions.\n                  <\/jats:p>","DOI":"10.1002\/2056-4538.70044","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:51:04Z","timestamp":1756993864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Myeloid sarcoma shows a high frequency of mutations activating the\n                    <scp>MAPK<\/scp>\n                    \/\n                    <scp>ERK<\/scp>\n                    pathway and association with clonal hematopoiesis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-793X","authenticated-orcid":false,"given":"Dominik","family":"Nann","sequence":"first","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim\u2010Colin","family":"Schade","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathis","family":"Overkamp","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejla","family":"Mahmutovic","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyyub","family":"Bag","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Forchhammer","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Slotta\u2010Huspenina","sequence":"additional","affiliation":[{"name":"Institute of Pathology Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar  Munich Germany"},{"name":"Institute of Pathology  Starnberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Boudova","sequence":"additional","affiliation":[{"name":"Biopticka Laboratory  Pilzen Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Sotlar","sequence":"additional","affiliation":[{"name":"Institute of Pathology Paracelsus Medical University  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-5365","authenticated-orcid":false,"given":"Leticia","family":"Quintanilla\u2010Martinez","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7732-0788","authenticated-orcid":false,"given":"Irina","family":"Bonzheim","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-293X","authenticated-orcid":false,"given":"Falko","family":"Fend","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology University Hospital Tuebingen and Comprehensive Cancer Center South West  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_8_3_1","first-page":"165","volume-title":"WHO Classification of Tumours: Haematolymphoid Tumours Part A","author":"Chen W","year":"2024"},{"key":"e_1_2_8_4_1","first-page":"245","volume-title":"The International Consensus Classification of Myeloid and Lymphoid Neoplasms","author":"Pizzi M","year":"2025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2023.04.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.5858\/2001-125-1448-CKCRIE"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245332.2017.1333275"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404491"},{"key":"e_1_2_8_9_1","first-page":"790","article-title":"Extramedullary myeloid cell tumors. An immunohistochemical study of 29 cases using routinely fixed and processed paraffin\u2010embedded tissue sections","volume":"119","author":"Roth MJ","year":"1995","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPO58YWIBUBESX"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.2208"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0083-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13056"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2021.102894"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/08880018.2020.1803462"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2020.06.009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1339879"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1225208"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2018.03.013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10831-7"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.7.1750.1750"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351518"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202321"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04313-x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2020.11.005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2019.11.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2023.2185091"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-875047"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-793620"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-023-03627-1"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0056-6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-024-01054-2"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2016.1.348"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.621"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-693879"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3343"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4247"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84708-6"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404699"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01368-1"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13038"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004983"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.196"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-011-0104-9"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2082-4"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01715349"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19060"}],"container-title":["The Journal of Pathology: Clinical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2056-4538.70044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:46:35Z","timestamp":1760305595000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/2056-4538.70044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/2056-4538.70044"],"URL":"https:\/\/doi.org\/10.1002\/2056-4538.70044","archive":["Portico"],"relation":{},"ISSN":["2056-4538","2056-4538"],"issn-type":[{"value":"2056-4538","type":"print"},{"value":"2056-4538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70044"}}