{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:58:38Z","timestamp":1784865518468,"version":"3.55.0"},"reference-count":87,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,23]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Innate immunity is increasingly recognized as a driver of neurodegeneration, although pathogenic mechanisms are incompletely understood. Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplastic disorder caused by activating somatic mutations in MAPK pathway genes, most commonly BRAFV600E, in myeloid precursors. A subset of patients with LCH develop progressive neurodegeneration (LCH-ND). We generated a human induced pluripotent stem cell (iPSC) model from patients with somatic hematologic mosaicism for BRAFV600E. Brain macrophages\/microglia from LCH iPSCs exhibit unique disease-specific pathogenic features. Stepwise differentiation identified hematopoietic progenitors as hyperproliferative, whereas brain macrophages were apoptosis resistant. Through application of cerebral organoids and a humanized murine xenotransplantation model, we identify marked heterogeneity of differentiation potential within clonal BRAFV600E lines in vivo. This model phenocopied human-specific phenotypes, including dense basal ganglia foci of abnormal macrophages, marked neurodegeneration with astrogliosis, and progressive ataxia. This approach will allow for preclinical testing of therapeutics for LCH-ND.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025032207","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:06:17Z","timestamp":1774980377000},"page":"433-449","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["Pathogenic myeloid phenotypes drive disease pathology in a novel human neurohistiocytosis model"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-419X","authenticated-orcid":false,"given":"Shivakumar","family":"Rajamanickam","sequence":"first","affiliation":[{"name":"1Department of Pediatrics, University of California San Diego, La Jolla, CA"},{"name":"2Sanford Consortium for Regenerative Medicine, La Jolla, 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Medicine, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Ding","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-6422","authenticated-orcid":false,"given":"Jennifer","family":"Picarsic","sequence":"additional","affiliation":[{"name":"3Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA"},{"name":"4Division of Pediatric Pathology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Glass","sequence":"additional","affiliation":[{"name":"5Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl 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