{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:05:11Z","timestamp":1774983911550,"version":"3.50.1"},"reference-count":121,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Janus kinase (JAK) inhibition forms the cornerstone of the treatment of myelofibrosis (MF), and the JAK inhibitor ruxolitinib is often used as a second-line agent in patients with polycythemia vera (PV) who fail hydroxyurea (HU). In addition, ruxolitinib continues to be studied in patients with essential thrombocythemia (ET). The benefits of JAK inhibition in terms of splenomegaly and symptoms in patients with MF are undeniable, and ruxolitinib prolongs the survival of persons with higher risk MF. Despite this, however, \u201cdisease-modifying\u201d effects of JAK inhibitors in MF, i.e., bone marrow fibrosis and mutant allele burden reduction, are limited. Similarly, in HU-resistant\/intolerant PV, while ruxolitinib provides excellent control of the hematocrit, symptoms and splenomegaly, reduction in the rate of thromboembolic events has not been convincingly demonstrated. Furthermore, JAK inhibitors do not prevent disease evolution to MF or acute myeloid leukemia (AML). Frontline cytoreductive therapy for PV generally comprises HU and interferons, which have their own limitations. Numerous novel agents, representing diverse mechanisms of action, are in development for the treatment of these three classic myeloproliferative neoplasms (MPNs). JAK inhibitor-based combinations, all of which are currently under study for MF, have been covered elsewhere in this issue. In this article, we focus on agents that have been studied as monotherapy in patients with MF, generally after JAK inhibitor resistance\/intolerance, as well as several novel compounds in development for PV\/ET.<\/jats:p>","DOI":"10.3390\/cancers12102891","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T21:42:21Z","timestamp":1602798141000},"page":"2891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel Concepts of Treatment for Patients with Myelofibrosis and Related Neoplasms"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-5712","authenticated-orcid":false,"given":"Prithviraj","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Masarova","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srdan","family":"Verstovsek","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1182\/blood-2014-02-554634","article-title":"Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis","volume":"123","author":"Rampal","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1182\/blood-2017-04-742288","article-title":"JAK2 inhibitors for myeloproliferative neoplasms: What is next?","volume":"130","author":"Bose","year":"2017","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1182\/blood-2018-01-791491","article-title":"The role of JAK2 inhibitors in MPNs 7 years after approval","volume":"131","author":"Passamonti","year":"2018","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMoa1110557","article-title":"A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis","volume":"366","author":"Verstovsek","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMoa1110556","article-title":"JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","volume":"366","author":"Harrison","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/jamaoncol.2015.1590","article-title":"Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: A randomized clinical trial","volume":"1","author":"Pardanani","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13045-017-0527-7","article-title":"Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses","volume":"10","author":"Verstovsek","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/leu.2016.148","article-title":"Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis","volume":"30","author":"Harrison","year":"2016","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1182\/blood-2015-03-635235","article-title":"The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis","volume":"126","author":"Deininger","year":"2015","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1182\/blood-2017-05-783225","article-title":"Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation","volume":"130","author":"Newberry","year":"2017","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00277-017-3194-4","article-title":"Between a rux and a hard place: Evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation","volume":"97","author":"Kuykendall","year":"2018","journal-title":"Ann. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/cncr.32664","article-title":"Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis","volume":"126","author":"Palandri","year":"2020","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1200\/JCO.2017.73.4418","article-title":"SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor-naive patients with myelofibrosis","volume":"35","author":"Mesa","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S2352-3026(17)30237-5","article-title":"Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): A randomised, open-label, phase 3 trial","volume":"5","author":"Harrison","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S2352-3026(17)30027-3","article-title":"Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): An international, randomised, phase 3 trial","volume":"4","author":"Mesa","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1001\/jamaoncol.2017.5818","article-title":"Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: A randomized clinical trial","volume":"4","author":"Mascarenhas","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1182\/blood-2016-09-740092","article-title":"Momelotinib inhibits ACVR1\/ALK2, decreases hepcidin production and ameliorates anemia of chronic disease in rodents","volume":"129","author":"Asshoff","year":"2017","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1182\/blood-2019-129293","article-title":"Results of PAC203: A randomized phase 2 dose-finding study and determination of the recommended dose of pacritinib in patients with myelofibrosis","volume":"134","author":"Gerds","year":"2019","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kuykendall, A., Horvat, N.P., Pandey, G., Komrokji, R.S., and Reuther, G.W. (2020). Finding a jill for JAK: Assessing past, present and future JAK inhibitor combination approaches in myelofibrosis. Cancers Basel, 12.","DOI":"10.3390\/cancers12082278"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1182\/blood-2018-99-111946","article-title":"Results of the myeloproliferative neoplasms-research consortium (MPN-RC) 112 randomized trial of pegylated interferon alfa-2a (PEG) versus hydroxyurea (HU) therapy for the treatment of high risk polycythemia vera (PV) and high risk essential thrombocythemia (ET)","volume":"132","author":"Mascarenhas","year":"2018","journal-title":"Blood"},{"key":"ref_21","unstructured":"European Medicines Agency (2019, August 30). Besremi. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/besremi."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1056\/NEJMoa1409002","article-title":"Ruxolitinib versus standard therapy for the treatment of polycythemia vera","volume":"372","author":"Vannucchi","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1470-2045(16)30558-7","article-title":"Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): A randomised, open-label, phase 3b study","volume":"18","author":"Passamonti","year":"2017","journal-title":"Lancet. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1182\/blood.2019000428","article-title":"Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea","volume":"134","author":"Yacoub","year":"2019","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1182\/bloodadvances.2019001158","article-title":"Ruxolitinib for the prevention of thrombosis in polycythemia vera: A systematic review and meta-analysis","volume":"4","author":"Masciulli","year":"2020","journal-title":"Blood Adv."},{"key":"ref_26","first-page":"184","article-title":"Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study","volume":"7","author":"Kiladjian","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/ajh.24851","article-title":"A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A propensity-matched study","volume":"92","author":"Barbui","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41408-018-0151-y","article-title":"Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases","volume":"8","author":"Rossi","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.amjmed.2004.06.032","article-title":"Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia","volume":"117","author":"Passamonti","year":"2004","journal-title":"Am. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1200\/JCO.2007.15.3569","article-title":"Leukocytosis and risk stratification assessment in essential thrombocythemia","volume":"26","author":"Carobbio","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5857","DOI":"10.1182\/blood-2011-02-339002","article-title":"Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: An international study of 891 patients","volume":"117","author":"Carobbio","year":"2011","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1182\/blood-2012-04-424911","article-title":"Correlation of blood counts with vascular complications in essential thrombocythemia: Analysis of the prospective PT1 cohort","volume":"120","author":"Campbell","year":"2012","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1056\/NEJMoa043800","article-title":"Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia","volume":"353","author":"Harrison","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1182\/blood-2012-07-443770","article-title":"Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: The ANAHYDRET Study, a randomized controlled trial","volume":"121","author":"Gisslinger","year":"2013","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1056\/NEJMcp1816082","article-title":"Essential thrombocythemia","volume":"381","author":"Tefferi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1182\/blood-2017-05-785790","article-title":"Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial","volume":"130","author":"Harrison","year":"2017","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1182\/blood-2017-02-765032","article-title":"Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: Long-term phase 2 study results","volume":"130","author":"Verstovsek","year":"2017","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1056\/NEJMoa1310523","article-title":"A pilot study of the telomerase inhibitor imetelstat for myelofibrosis","volume":"373","author":"Tefferi","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1182\/bloodadvances.2018022012","article-title":"Imetelstat, a telomerase inhibitor, is capable of depleting myelofibrosis stem and progenitor cells","volume":"2","author":"Wang","year":"2018","journal-title":"Blood Adv."},{"key":"ref_40","first-page":"1107","article-title":"Favorable overall survival with imetelstat treatment correlates with other clinical benefits in intermediate 2 or high risk myelofibrosis relapsed\/refractory to janus kinase inhibitor","volume":"4","author":"Mascarenhas","year":"2020","journal-title":"Hemasphere"},{"key":"ref_41","first-page":"1098","article-title":"Telomerase activity, telomere length and htert expression correlate with clinical outcomes in higher risk myelofibrosis (mf) relapsed\/refractory (r\/r) to janus kinase inhibitor treated with imetelstat","volume":"4","author":"Mascarenhas","year":"2020","journal-title":"Hemasphere"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1182\/blood-2014-05-578435","article-title":"Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis","volume":"124","author":"Rumi","year":"2014","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/leu.2014.3","article-title":"CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons","volume":"28","author":"Tefferi","year":"2014","journal-title":"Leukemia"},{"key":"ref_44","first-page":"1101","article-title":"Imetelstat treatment results in clinical benefits, including improved overall survival, in patients with higher-risk triple-negative myelofibrosis relapsed\/refractory to janus kinase inhibitors (jaki)","volume":"4","author":"Kiladjian","year":"2020","journal-title":"Hemasphere"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1056\/NEJMoa1503479","article-title":"Telomerase inhibitor imetelstat in patients with essential thrombocythemia","volume":"373","author":"Baerlocher","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1084\/jem.20160283","article-title":"Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis","volume":"213","author":"Verstovsek","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1038\/leu.2017.112","article-title":"Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis","volume":"31","author":"Maekawa","year":"2017","journal-title":"Leukemia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1182\/blood.2019000051","article-title":"Increased SLAMF7(high) monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab","volume":"134","author":"Maekawa","year":"2019","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.stem.2017.03.008","article-title":"Gli1+ mesenchymal stromal cells are a key driver of bone marrow fibrosis and an important cellular therapeutic target","volume":"20","author":"Schneider","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_50","first-page":"5","article-title":"Bone marrow fibrosis in primary myelofibrosis: Pathogenic mechanisms and the role of TGF-beta","volume":"3","author":"Agarwal","year":"2016","journal-title":"Stem Cell Investig."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ozono, Y., Shide, K., Kameda, T., Kamiunten, A., Tahira, Y., Sekine, M., Akizuki, K., Nakamura, K., Iwakiri, H., and Sueta, M. (2020). Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice. Leukemia.","DOI":"10.1038\/s41375-020-0880-3"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1358\/dnp.2010.23.5.1444206","article-title":"PRM-151 (recombinant human serum amyloid P\/pentraxin 2) for the treatment of fibrosis","volume":"23","author":"Duffield","year":"2010","journal-title":"Drug News Perspect."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1182\/blood-2018-99-115362","article-title":"PRM-151 in myelofibrosis: Efficacy and safety in an open label extension study","volume":"132","author":"Verstovsek","year":"2018","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1097\/01.HS9.0000561592.51072.9b","article-title":"A randomized, double blind phase 2 study of 3 different doses of prm-151 in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib","volume":"3","author":"Verstovsek","year":"2019","journal-title":"Hemasphere"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/bjh.14501","article-title":"A phase 2 study of simtuzumab in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis","volume":"176","author":"Verstovsek","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1038\/nm.3995","article-title":"Targeting megakaryocytic-induced fibrosis in myeloproliferative neoplasms by AURKA inhibition","volume":"21","author":"Wen","year":"2015","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1158\/1078-0432.CCR-19-1005","article-title":"Aurora Kinase a inhibition provides clinical benefit, normalizes megakaryocytes, and reduces bone marrow fibrosis in patients with myelofibrosis","volume":"25","author":"Gangat","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1182\/blood-2013-03-488098","article-title":"Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report","volume":"122","author":"Tefferi","year":"2013","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI82905","article-title":"Downregulation of GATA1 drives impaired hematopoiesis in primary myelofibrosis","volume":"127","author":"Gilles","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1038\/bcj.2017.51","article-title":"The thrombopoietin\/MPL axis is activated in the Gata1(low) mouse model of myelofibrosis and is associated with a defective RPS14 signature","volume":"7","author":"Zingariello","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1182\/blood-2012-06-439661","article-title":"Characterization of the TGF-beta1 signaling abnormalities in the Gata1low mouse model of myelofibrosis","volume":"121","author":"Zingariello","year":"2013","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1182\/bloodadvances.2016000208","article-title":"Targeted deep sequencing in primary myelofibrosis","volume":"1","author":"Tefferi","year":"2016","journal-title":"Blood Adv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1182\/bloodadvances.2016000216","article-title":"Targeted deep sequencing in polycythemia vera and essential thrombocythemia","volume":"1","author":"Tefferi","year":"2016","journal-title":"Blood Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1056\/NEJMc1012718","article-title":"P53 lesions in leukemic transformation","volume":"364","author":"Harutyunyan","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E5401","DOI":"10.1073\/pnas.1407792111","article-title":"Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms","volume":"111","author":"Rampal","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/onc.2011.313","article-title":"JAK2(V617F) negatively regulates p53 stabilization by enhancing MDM2 via la expression in myeloproliferative neoplasms","volume":"31","author":"Nakatake","year":"2012","journal-title":"Oncogene"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1182\/blood-2013-11-536854","article-title":"The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon alpha 2a target JAK2V617F-positive progenitor and stem cells","volume":"124","author":"Lu","year":"2014","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1182\/blood.2018893545","article-title":"Oral idasanutlin in patients with polycythemia vera","volume":"134","author":"Mascarenhas","year":"2019","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1182\/blood-2013-01-478891","article-title":"Revised response criteria for polycythemia vera and essential thrombocythemia: An ELN and IWG-MRT consensus project","volume":"121","author":"Barosi","year":"2013","journal-title":"Blood"},{"key":"ref_70","first-page":"215","article-title":"KRT-232, A first-in-class, murine double minute 2 inhibitor, for myelofibrosis relapsed or refractory to janus-associated kinase inhibitor treatment","volume":"4","author":"Delgado","year":"2020","journal-title":"Hemasphere"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/leu.2008.91","article-title":"A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia\/polycythemia vera myelofibrosis","volume":"22","author":"Tong","year":"2008","journal-title":"Leukemia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.leukres.2012.03.003","article-title":"Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis","volume":"36","author":"Kantarjian","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/bjh.12220","article-title":"A phase I study of panobinostat (LBH589) in patients with primary myelofibrosis (PMF) and post-polycythaemia vera\/essential thrombocythaemia myelofibrosis (post-PV\/ET MF)","volume":"161","author":"Mascarenhas","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.leukres.2016.11.015","article-title":"A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera\/essential thrombocythemia myelofibrosis (post-PV\/ET MF)","volume":"53","author":"Mascarenhas","year":"2016","journal-title":"Leuk. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ccell.2017.11.009","article-title":"Dual targeting of oncogenic activation and inflammatory signaling increases therapeutic efficacy in myeloproliferative neoplasms","volume":"33","author":"Kleppe","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_76","first-page":"1084","article-title":"CPI-0610, a bromodomain and extraterminal domain protein (bet) inhibitor, in combination with ruxolitinib, in jak inhibitor treatment na\u00efve myelofibrosis patients: Update from manifest phase 2 study","volume":"4","author":"Mascarenhas","year":"2020","journal-title":"Haemasphere"},{"key":"ref_77","first-page":"1083","article-title":"CPI-0610, bromodomain and extraterminal domain protein (bet) inhibitor, as \u2019add-on\u2019 to ruxolitinib (rux), in advanced myelofibrosis patients with suboptimal response: Update of manifest phase 2 study","volume":"4","author":"Verstovsek","year":"2020","journal-title":"Haemasphere"},{"key":"ref_78","first-page":"1091","article-title":"CPI-0610, a bromodomain and extraterminal domain protein (BET) inhibitor, as monotherapy in advanced myelofibrosis patients refractory\/intolerant to JAK inhibitor: Update from phase 2 MANIFEST study","volume":"4","author":"Talpaz","year":"2020","journal-title":"Hemasphere"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1182\/blood.V126.23.601.601","article-title":"Lysine-specific histone demethylase, LSD1, (KDM1A) as a novel therapeutic target in myeloproliferative neoplasms","volume":"126","author":"Kleppe","year":"2015","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/HS9.0000000000000054","article-title":"LSD1 Inhibition prolongs survival in mouse models of MPN by selectively targeting the disease clone","volume":"2","author":"Jutzi","year":"2018","journal-title":"Hemasphere"},{"key":"ref_81","first-page":"1080","article-title":"A phase 2 study of bomedemstat (IMG-7289), a lysine-specific demethylase-1 (LSD1) inhibitor, for the treatment of myelofibrosis (MF)","volume":"4","author":"Pettit","year":"2020","journal-title":"Hemasphere"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Pastore, F., Bhagwat, N., Pastore, A., Radzisheuskaya, A., Karzai, A., Krishnan, A., Li, B., Bowman, R.L., Xiao, W., and Viny, A.D. (2020). PRMT5 inhibition modulates E2F1 methylation and gene regulatory networks leading to therapeutic efficacy in JAK2V617F mutant MPN. Cancer Discov.","DOI":"10.1158\/2159-8290.CD-20-0026"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.celrep.2013.10.038","article-title":"Combined targeting of JAK2 and Bcl-2\/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors","volume":"5","author":"Waibel","year":"2013","journal-title":"Cell Rep."},{"key":"ref_84","first-page":"1081","article-title":"Navitoclax in combination with ruxolitinib in patients with primary or secondary myelofibrosis: A phase 2 study","volume":"4","author":"Harrison","year":"2020","journal-title":"Haemasphere"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.cell.2007.01.037","article-title":"Programmed anuclear cell death delimits platelet life span","volume":"128","author":"Mason","year":"2007","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S1470-2045(10)70261-8","article-title":"Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: A phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity","volume":"11","author":"Wilson","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1200\/JCO.2010.31.6208","article-title":"Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors","volume":"29","author":"Gandhi","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1200\/JCO.2011.34.7898","article-title":"Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: Results of a phase I study of navitoclax in patients with relapsed or refractory disease","volume":"30","author":"Roberts","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1158\/1078-0432.CCR-11-3090","article-title":"Phase 2 study of single agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer","volume":"18","author":"Rudin","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nm.3048","article-title":"ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets","volume":"19","author":"Souers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1101\/gad.12.16.2475","article-title":"Selective regulation of Bcl-XL by a Jak kinase-dependent pathway is bypassed in murine hematopoietic malignancies","volume":"12","author":"Packham","year":"1998","journal-title":"Genes Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10978","DOI":"10.1111\/jcmm.15730","article-title":"Bcl-xL represents a therapeutic target in Philadelphia negative myeloproliferative neoplasms","volume":"24","author":"Petiti","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1182\/blood-2011-04-348144","article-title":"TNFalpha facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms","volume":"118","author":"Fleischman","year":"2011","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1038\/s41375-018-0131-z","article-title":"Autocrine Tnf signaling favors malignant cells in myelofibrosis in a Tnfr2-dependent fashion","volume":"32","author":"Heaton","year":"2018","journal-title":"Leukemia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1182\/blood-2019-130046","article-title":"Final Results of Phase 2 Clinical Trial of LCL161, a Novel Oral SMAC Mimetic\/IAP Antagonist for Patients with Intermediate to High Risk Myelofibrosis","volume":"134","author":"Pemmaraju","year":"2019","journal-title":"Blood"},{"key":"ref_96","first-page":"218","article-title":"Updated results from a phase 1\/2 clinical trial of tagraxofusp, a CD123-targeted therapy, in patients with poor-risk myelofibrosis","volume":"4","author":"Pemmaraju","year":"2020","journal-title":"Hemasphere"},{"key":"ref_97","first-page":"14","article-title":"Nuclear-cytoplasmic transport is a therapeutic target in myelofibrosis","volume":"25","author":"Yan","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.leukres.2019.02.010","article-title":"Programmed cell death receptor (PD-1) ligand (PD-L1) expression in Philadelphia chromosome-negative myeloproliferative neoplasms","volume":"79","author":"Wang","year":"2019","journal-title":"Leuk. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1158\/2159-8290.CD-18-1356","article-title":"Immune checkpoint blockade enhances shared neoantigen-induced T-cell immunity directed against mutated calreticulin in myeloproliferative neoplasms","volume":"9","author":"Roudko","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1182\/blood-2015-04-637280","article-title":"Ropeginterferon alfa-2b, a novel IFNalpha-2b, induces high response rates with low toxicity in patients with polycythemia vera","volume":"126","author":"Gisslinger","year":"2015","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1182\/blood-2018-99-118584","article-title":"Long-Term efficacy and safety of ropeginterferon alfa-2b in patients with polycythemia vera\u2014Final phase I\/II peginvera study results","volume":"132","author":"Gisslinger","year":"2018","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S2352-3026(19)30236-4","article-title":"Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): A randomised, non-inferiority, phase 3 trial and its extension study","volume":"7","author":"Gisslinger","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1182\/blood-2019-122233","article-title":"Thromboembolic risk reduction and high rate of complete molecular response with long-term use of ropeginterferon alpha-2b in polycythemia vera: Results from a randomized controlled study","volume":"134","author":"Kiladjian","year":"2019","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1182\/blood-2018-99-119268","article-title":"Effect of ropeginterferon alfa-2b in prefibrotic primary myelofibrosis","volume":"132","author":"Gisslinger","year":"2018","journal-title":"Blood"},{"key":"ref_105","first-page":"2602","article-title":"Phase II randomized clinical trial comparing ropeginterferon versus phlebotomy in low-risk patients with polycythemia vera. results of the pre-planned interim analysis","volume":"4","author":"Barbui","year":"2020","journal-title":"Hemasphere"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1080\/13543784.2016.1250882","article-title":"Investigational histone deacetylase inhibitors (HDACi) in myeloproliferative neoplasms","volume":"25","author":"Bose","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/13543784.2020.1761323","article-title":"Givinostat: An emerging treatment for polycythemia vera","volume":"29","author":"Chifotides","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/sj.leu.2405049","article-title":"The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F)","volume":"22","author":"Guerini","year":"2008","journal-title":"Leukemia"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.exphem.2012.10.013","article-title":"Associazione Italiana per la Ricerca sul Cancro-Gruppo Italiano Malattie Mieloproliferative Investigators. Givinostat and hydroxyurea synergize in vitro to induce apoptosis of cells from JAK2(V617F) myeloproliferative neoplasm patients","volume":"41","author":"Calzada","year":"2013","journal-title":"Exp. Hematol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/bjh.12332","article-title":"A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy","volume":"161","author":"Finazzi","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1038\/s41375-020-0735-y","article-title":"Safety and efficacy of the maximum tolerated dose of givinostat in polycythemia vera: A two-part Phase Ib\/II study","volume":"34","author":"Rambaldi","year":"2020","journal-title":"Leukemia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1038\/s41375-018-0207-9","article-title":"Dysregulated iron metabolism in polycythemia vera: Etiology and consequences","volume":"32","author":"Ginzburg","year":"2018","journal-title":"Leukemia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1182\/blood-2019-122546","article-title":"A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia","volume":"134","author":"Gerds","year":"2019","journal-title":"Blood"},{"key":"ref_114","first-page":"15","article-title":"MIPSS70: Mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis","volume":"36","author":"Guglielmelli","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1200\/JCO.2018.78.9867","article-title":"MIPSS70+ Version 2.0: Mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis","volume":"36","author":"Tefferi","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41375-018-0107-z","article-title":"GIPSS: Genetically inspired prognostic scoring system for primary myelofibrosis","volume":"32","author":"Tefferi","year":"2018","journal-title":"Leukemia"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/bjh.16380","article-title":"Mutation-enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera","volume":"189","author":"Tefferi","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1182\/blood-2015-03-633404","article-title":"Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib","volume":"126","author":"Patel","year":"2015","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJMc0910063","article-title":"Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms","volume":"362","author":"Green","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/leu.2010.77","article-title":"IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms","volume":"24","author":"Pardanani","year":"2010","journal-title":"Leukemia"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/bjh.16709","article-title":"Clinical outcomes of IDH2-mutated advanced-phase Ph-negative myeloproliferative neoplasms treated with enasidenib","volume":"190","author":"Patel","year":"2020","journal-title":"Br. J. Haematol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:17:47Z","timestamp":1760177867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/10\/2891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,9]]},"references-count":121,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cancers12102891"],"URL":"https:\/\/doi.org\/10.3390\/cancers12102891","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,9]]}}}