{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:35:13Z","timestamp":1760189713793},"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":[[2019,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share a common pathobiology of constitutive activation of the JAK and STAT pathway, despite having the 3 distinct phenotypes of essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Targeting the JAK-STAT pathway has led to remarkable clinical benefit, including reduction in splenomegaly, amelioration of cytokine-driven symptoms, improvement in quality of life, and even some improvement in survival. However, targeting this pathway has not resulted in consistent disease modification by current metrics, including a reduction in mutant allele burden or reversal of fibrosis. Moreover, targeting JAK-STAT can lead to limiting treatment-emergent side effects, such as anemia and thrombocytopenia. Continued discovery points to a complex system of pathogenesis beyond JAK-STAT driving the formation and evolution of MPNs. This article reviews the successes and limitations of JAK-STAT inhibition, surveys the strategies behind emerging therapies, and discusses the challenges that are present in moving beyond JAK-STAT.<\/jats:p>","DOI":"10.1182\/hematology.2019000048","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T15:14:23Z","timestamp":1575645263000},"page":"407-414","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":11,"title":["Beyond JAK-STAT: novel therapeutic targets in Ph-negative MPN"],"prefix":"10.1182","volume":"2019","author":[{"given":"Aaron T.","family":"Gerds","sequence":"first","affiliation":[{"name":"Leukemia and Myeloid Disorders Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019120610104812700_B1","volume-title":"Dancing in the dark. 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