{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:05:55Z","timestamp":1791338755464,"version":"4.3.1"},"reference-count":58,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The identification of JAK2V617F mutations in polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) represents an important advance in our understanding of these myeloproliferative disorders (MPD). Most, if not all, patients with PV and a significant number of patients with ET and MF are JAK2V617F positive, and the mutation likely arises in the hematopoietic stem cell compartment. JAK2V617F is a constitutively active tyrosine kinase that is able to activate JAK-STAT signaling most efficiently when co-expressed with the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte colony-stimulating factor receptor (GCSFR). Data from murine models supports the central role of JAK2V617F in the pathogenesis of MPD, as expression of JAK2V617F in a bone marrow transplantation assay results in polycythemia and myelofibrosis in recipient mice. Activation of JAK-STAT signaling by JAK2V617F in some, but not all MPD patients with ET and MF led to the identification of the constitutively active MPLW515L allele in ET and MF. Small molecule inhibitors of JAK-STAT signaling are currently being developed, which offer potential for molecularly targeted therapy for patients with PV, ET, and MF. Despite these advances, many questions remain regarding the role of a single disease allele in three phenotypically distinct MPD, the potential clinical efficacy of JAK2 inhibitors, and the identity of oncogenic alleles in JAK2V617F\/MPLW515-negative MPD.<\/jats:p>","DOI":"10.1182\/asheducation-2006.1.233","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T23:14:02Z","timestamp":1164237242000},"page":"233-239","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":45,"title":["Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders"],"prefix":"10.1182","volume":"2006","author":[{"given":"Ross L.","family":"Levine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerlinde","family":"Wernig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111703412240200_R1","doi-asserted-by":"crossref","unstructured":"Dameshek W. 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The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. 2005;106:3377\u20133379.","DOI":"10.1182\/blood-2005-05-1898"},{"key":"2019111703412240200_R11","doi-asserted-by":"crossref","unstructured":"Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both \u201catypical\u201d myeloproliferative disorders and the myelodysplastic syndrome. Blood. 2005;106:1207\u20131209.","DOI":"10.1182\/blood-2005-03-1183"},{"key":"2019111703412240200_R12","doi-asserted-by":"crossref","unstructured":"Verma A, Kambhampati S, Parmar S, Platanias LC. Jak family of kinases in cancer. Cancer Metastasis Rev. 2003;22:423\u2013434.","DOI":"10.1023\/A:1023805715476"},{"key":"2019111703412240200_R13","doi-asserted-by":"crossref","unstructured":"Scott LM, Campbell PJ, Baxter EJ, et al. 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