{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:15:59Z","timestamp":1790846159751,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,18]],"date-time":"2018-03-18T00:00:00Z","timestamp":1521331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myelofibrosis (MF) is a clinical manifestation of chronic BCR-ABL1-negative chronic myeloproliferative neoplasms. Splenomegaly is one of the major clinical manifestations of MF and is directly linked to splenic extramedullary hematopoiesis (EMH). EMH is associated with abnormal trafficking patterns of clonal hematopoietic cells due to the dysregulated bone marrow (BM) microenvironment leading to progressive splenomegaly. Several recent data have emphasized the role of several cytokines for splenic EMH. Alteration of CXCL12\/CXCR4 pathway could also lead to splenic EMH by migrated clonal hematopoietic cells from BM to the spleen. Moreover, low Gata1 expression was found to be significantly associated with the EMH. Several gene mutations were found to be associated with significant splenomegaly in MF. In recent data, JAK2 V617F homozygous mutation was associated with a larger spleen size. In other data, CALR mutations in MF were signigicantly associated with longer larger splenomegaly-free survivals than others. In addition, MF patients with \u22651 mutations in AZXL1, EZH1 or IDH1\/2 had significantly low spleen reduction response in ruxolitinib treatment. Developments of JAK inhibitors, such as ruxolitinib, pacritinib, momelotinib, and febratinib enabled the effective management in MF patients. Especially, significant spleen reduction responses of the drugs were demonstrated in several randomized clinical studies, although those could not eradicate allele burdens of MF.<\/jats:p>","DOI":"10.3390\/ijms19030898","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T06:57:11Z","timestamp":1521529031000},"page":"898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Understanding Splenomegaly in Myelofibrosis: Association with Molecular Pathogenesis"],"prefix":"10.3390","volume":"19","author":[{"given":"Moo-Kon","family":"Song","sequence":"first","affiliation":[{"name":"Department of Hematology-Oncology, Hanyang University Hanmaeum Changwon Hospital, Changwon 51497, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Bae","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Hospital, 222-1, Seongdong-Gu Wangsimni-Ro, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Uhm","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Hospital, 222-1, Seongdong-Gu Wangsimni-Ro, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1182\/blood-2007-04-083501","article-title":"Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: Recommendations from an ad hoc international expert panel","volume":"110","author":"Tefferi","year":"2007","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1182\/blood.V51.2.189.189","article-title":"Agnogenic myeloid metaplasia: A clonal proliferation of hematopoietic stem cells with secondary myelofibrosis","volume":"51","author":"Jacobson","year":"1978","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1200\/JCO.1999.17.9.2954","article-title":"Myelofibrosis with myeloid metaplasia: Diagnostic definition and prognostic classification for clinical studies and treatment guidelines","volume":"17","author":"Barosi","year":"1999","journal-title":"J. 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