{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:15:04Z","timestamp":1787652904178,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["T32CA009357"],"award-info":[{"award-number":["T32CA009357"]}]},{"name":"National Institute of Health","award":["R01HL150707"],"award-info":[{"award-number":["R01HL150707"]}]},{"name":"National Institute of Health","award":["T32CA009357"],"award-info":[{"award-number":["T32CA009357"]}]},{"name":"National Institute of Health","award":["R01HL150707"],"award-info":[{"award-number":["R01HL150707"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations in JAK2, MPL, and CALR, which manifests as hyperactive Jak\/Stat signaling. Triple-negative MF is diagnosed in the absence of JAK2, MPL, and CALR but when clinical, morphologic criteria are met and other mutation(s) is\/are present, including ASXL1, EZH2, and SRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras\/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response. KRAS and NRAS mutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such as CBL, NF1, BRAF, and PTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence of RAS and related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets.<\/jats:p>","DOI":"10.3390\/cancers15184654","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T21:47:03Z","timestamp":1695246423000},"page":"4654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-183X","authenticated-orcid":false,"given":"Samuel B.","family":"Reynolds","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Pettit","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malathi","family":"Kandarpa","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Talpaz","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/ajh.26050","article-title":"Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management","volume":"96","author":"Tefferi","year":"2021","journal-title":"Am. 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