{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:39:40Z","timestamp":1790746780916,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T00:00:00Z","timestamp":1445558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","award":["P01-CA108671"],"award-info":[{"award-number":["P01-CA108671"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Brian Rooney Fund of the Lymphoma Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Splenomegaly is a major manifestation of primary myelofibrosis (PMF) contributing to clinical symptoms and hematologic abnormalities. The spleen from PMF patients contains increased numbers of hematopoietic stem cells (HSC) and megakaryocytes (MK). These MK express high levels of P-selectin (P-sel) that, by triggering neutrophil emperipolesis, may cause TGF-\u03b2 release and disease progression. This hypothesis was tested by deleting the P-sel gene in the myelofibrosis mouse model carrying the hypomorphic Gata1low mutation that induces megakaryocyte abnormalities that recapitulate those observed in PMF. P-selnullGata1low mice survived splenectomy and lived 3 months longer than P-selWTGata1low littermates and expressed limited fibrosis and osteosclerosis in the marrow or splenomegaly. Furthermore, deletion of P-sel disrupted megakaryocyte\/neutrophil interactions in spleen, reduced TGF-\u03b2 content, and corrected the HSC distribution that in Gata1low mice, as in PMF patients, is abnormally expanded in spleen. Conversely, pharmacological inhibition of TGF-\u03b2 reduced P-sel expression in MK and corrected HSC distribution. Spleens, but not marrow, of Gata1low mice contained numerous cKITpos activated fibrocytes, probably of dendritic cell origin, whose membrane protrusions interacted with MK establishing niches hosting immature cKITpos hematopoietic cells. These activated fibrocytes were not detected in spleens from P-selnullGata1low or TGF-\u03b2-inhibited Gata1low littermates and were observed in spleen, but not in marrow, from PMF patients. Therefore, in Gata1low mice, and possibly in PMF, abnormal P-sel expression in MK may mediate the pathological cell interactions that increase TGF-\u03b2 content in MK and favor establishment of a microenvironment that supports myelofibrosis-related HSC in spleen.<\/jats:p>","DOI":"10.1002\/stem.2229","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T11:44:41Z","timestamp":1444131881000},"page":"67-82","source":"Crossref","is-referenced-by-count":39,"title":["P-Selectin Sustains Extramedullary Hematopoiesis in the\n                    <i>G<\/i>\n                    <i>ata1low<\/i>\n                    Model of Myelofibrosis"],"prefix":"10.1093","volume":"34","author":[{"given":"Gerald J.","family":"Spangrude","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"CEA\/DSV\/iRCM\/LRTS, Inserm U967, Fontenay-aux-Roses Cedex, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zingariello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Campus Biomedico, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sancillo","sequence":"additional","affiliation":[{"name":"Istituto Genetica Medica, Centro Nazionale Ricerche, and Medicine and Aging Sciences, Section of Human Momorphology, University G. D'Annunzio, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Alba","family":"Rana","sequence":"additional","affiliation":[{"name":"Istituto Genetica Medica, Centro Nazionale Ricerche, and Medicine and Aging Sciences, Section of Human Momorphology, University G. D'Annunzio, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Migliaccio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Alma Mater University, Bologna, Italy"},{"name":"Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,23]]},"reference":[{"key":"2022010523154904700_stem2229-bib-0001","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1056\/NEJM200004273421706","article-title":"Myelofibrosis with myeloid metaplasia","volume":"342","author":"Tefferi","year":"2000","journal-title":"N Engl J Med"},{"key":"2022010523154904700_stem2229-bib-0002","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.3324\/haematol.2013.086348","article-title":"Advances in myelofibrosis: A clinical case 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