{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:55:54Z","timestamp":1787162154181,"version":"build-2736575974"},"reference-count":21,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation. Unlike pediatric HLH, adult HLH is rarely driven by germline genetic variants. Although numerous precipitating etiologies have been identified, the reason that HLH occurs in only a subset of individuals and how other factors contribute to the disease remains unknown. We hypothesized that clonal hematopoiesis (CH), a state in which somatic mutations in blood cells cause an expanded population of mutant hematopoietic cells and drive an aberrant inflammatory state, could contribute to adult-onset HLH. In a highly annotated cohort of older adults with HLH we found that CH was more prevalent than in control cohorts. Using the adult-onset HLH mouse model in which repeated treatments of the TLR9 agonist, ODN1826, was delivered to the mouse, we observed that macrophages carrying mutations in Tet2, one of the most commonly mutated genes in CH, have an enhanced inflammatory response to TLR9 agonism. Finally, mice carrying Tet2 mutations in the hematopoietic compartment (a common model for CH) displayed an exaggerated response to TLR9 agonism, including worse splenomegaly and anemia. Our data suggest that CH is more common in individuals with adult-onset HLH and can contribute to the pathophysiology of this disease.<\/jats:p>","DOI":"10.1182\/blood.2020008206","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T19:46:29Z","timestamp":1600803989000},"page":"3051-3055","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":32,"title":["Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-9335","authenticated-orcid":false,"given":"Peter G.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"},{"name":"Division of Hematology, Department of Medicine, Brigham and Women\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Castellano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"McConkey","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ceremsak","sequence":"additional","affiliation":[{"name":"Harvard-MIT Program in Health Sciences and Technology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Birndt","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin II, Universit\u00e4tsklinikum Jena, Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Perner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Arnason","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mridul","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"},{"name":"Division of Hematology, Department of Medicine, Brigham and Women\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Schram","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Nikiforow","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German","family":"Pihan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Hasserjian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Aster","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-7809","authenticated-orcid":false,"given":"Paul","family":"La Ros\u00e9e","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany; 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