{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T20:10:45Z","timestamp":1794427845428,"version":"4.9.1"},"reference-count":49,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The mechanisms that lead to extramedullary tropism of acute myeloid leukemia (eAML) remain obscure and no specific therapeutic approaches for this entity exist. Because the long-term survival of eAML is poor, a deeper understanding of the immune microenvironment and leukemia phenotypes underlying this entity is warranted. Here, we performed bulk and single-cell transcriptome profiling of 23 eAML biopsies from 10 patients with isolated extramedullary disease in skin and subcutaneous tissue. Unlike normal healthy skin, we found leukemia cutis to be heavily immune infiltrated; in extramedullary relapse after allogeneic stem cell transplantation, &amp;gt;90% of T\/natural killer cells were donor derived. eAML-associated T cells expressed a clear signature of T-cell exhaustion, dissimilar to leukemia-associated immune populations in bone marrow relapse (n = 7) but related to acute and chronic skin inflammation. Furthermore, HLA class II was downregulated in 4 of 7 leukemia cutis specimens, consistent with an immune escape phenotype in eAML. Extramedullary and bone marrow\u2013resident leukemia cells differed with regard to the expression of 8 homing receptor molecules (ICAM1 [encoding CD54], PECAM1 [CD31], ITGA4, ITGA6, ITGAL, ITGB4, ITGA5, and ITGAV). Serial samples obtained from 1 leukemia cutis throughout consecutive immune checkpoint blockade with ipilimumab followed by nivolumab showed a consistently high degree of overlap between local and circulating T-cell receptor sequences, suggesting that only a minority of eAML-associated T cells are leukemia specific. Our analysis reveals eAML to associate with complex changes in leukemia and T-cell gene expression profiles that suggest multiple potential avenues for therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029121","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T19:05:11Z","timestamp":1759259111000},"page":"35-47","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["Mechanisms of immune escape and extramedullary tropism in leukemia cutis"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-0207","authenticated-orcid":false,"given":"Livius","family":"Penter","sequence":"first","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"2Department of Hematology, Oncology, and Cancer Immunology, Campus Virchow-Klinikum, Berlin, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"3Berlin Institute of Health Charit\u00e9 Digital Clinician Scientist Program, Berlin Institute of Health Biomedical Innovation Academy, Berlin Institute of Health at Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-181X","authenticated-orcid":false,"given":"Katie","family":"Maurer","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"4Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA"},{"name":"5Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-6272","authenticated-orcid":false,"given":"Nicoletta","family":"Cieri","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"4Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA"},{"name":"5Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5584-041X","authenticated-orcid":false,"given":"Wesley S.","family":"Lu","sequence":"additional","affiliation":[{"name":"6Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxiang","family":"Lyu","sequence":"additional","affiliation":[{"name":"6Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6194-8871","authenticated-orcid":false,"given":"Mischa","family":"Selig","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Oncology, and Cancer Immunology, Campus Virchow-Klinikum, Berlin, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Joosten","sequence":"additional","affiliation":[{"name":"7Institute of Pathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-1321","authenticated-orcid":false,"given":"Jana","family":"Ihlow","sequence":"additional","affiliation":[{"name":"3Berlin Institute of Health Charit\u00e9 Digital Clinician Scientist Program, Berlin Institute of Health Biomedical Innovation Academy, Berlin Institute of Health at Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"7Institute of Pathology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqiang","family":"Li","sequence":"additional","affiliation":[{"name":"4Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA"},{"name":"6Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9105-5856","authenticated-orcid":false,"given":"Kenneth J.","family":"Livak","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"6Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Oncology, and Cancer Immunology, Campus Virchow-Klinikum, Berlin, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-4669","authenticated-orcid":false,"given":"Jerome","family":"Ritz","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"5Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Bachireddy","sequence":"additional","affiliation":[{"name":"8MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Davids","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"5Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6302","authenticated-orcid":false,"given":"Jacqueline 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