{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:31:16Z","timestamp":1790483476372,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:00:00Z","timestamp":1539043200000},"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>Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers. Histone deacetylase inhibitors (HDACi) are epigenetic modifiers that, in vitro, have been shown to induce growth arrest, apoptotic or autophagic cell death, and terminal differentiation of myeloid tumor cells. These effects were observed both at the bulk tumor level and in the most immature CD34+38\u2212 cell compartments containing the leukemic stem cells. Thus, there is a strong rationale supporting HDACi therapy in myeloid malignancies. However, despite initial promising results in phase I trials, HDACi in monotherapy as well as in combination with other drugs, have failed to improve responses or survival. This review provides an overview of the rationale for HDACi in myeloid malignancies, clinical results and speculations on why clinical trials have thus far not met the expectations, and how this may be improved in the future.<\/jats:p>","DOI":"10.3390\/ijms19103091","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T11:10:44Z","timestamp":1539083444000},"page":"3091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors"],"prefix":"10.3390","volume":"19","author":[{"given":"Johanna S.","family":"Ungerstedt","sequence":"first","affiliation":[{"name":"Department of Medicine, Huddinge, Karolinska Institutet, and Hematology Center, and Karolinska University Hospital, S-141 86 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1053\/j.seminhematol.2017.06.001","article-title":"Optimizing the use of hypomethylating agents in myelodysplastic syndromes: Selecting the candidate, predicting the response, and enhancing the activity","volume":"54","author":"Madanat","year":"2017","journal-title":"Semin. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hagemann, S., Heil, O., Lyko, F., and Brueckner, B. (2011). Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017388"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1182\/blood.V100.8.2957","article-title":"Demethylation of a hypermethylated P15\/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2\u2032-deoxycytidine (decitabine) treatment","volume":"100","author":"Daskalakis","year":"2002","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.exphem.2007.10.002","article-title":"Hypomethylation and apoptosis in 5-azacytidine-treated myeloid cells","volume":"36","author":"Khan","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28812","DOI":"10.18632\/oncotarget.15807","article-title":"Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive\/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease","volume":"8","author":"Tobiasson","year":"2017","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.5966\/sctm.2014-0035","article-title":"Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome","volume":"3","author":"Wong","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e123","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_9","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1182\/blood-2009-09-245837","article-title":"A dynamic prognostic model to predict survival in primary myelofibrosis: A study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment)","volume":"115","author":"Passamonti","year":"2010","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1182\/blood-2014-07-575373","article-title":"How I treat myelofibrosis","volume":"124","author":"Cervantes","year":"2014","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1182\/blood-2017-04-736421","article-title":"How I treat chronic myelomonocytic leukemia","volume":"130","author":"Solary","year":"2017","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1056\/NEJMc1515403","article-title":"Midostaurin in Advanced Systemic Mastocytosis","volume":"374","author":"Chandesris","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1200\/JCO.2014.55.2018","article-title":"Hematopoietic stem-cell transplantation for advanced systemic mastocytosis","volume":"32","author":"Ustun","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/bcj.2016.50","article-title":"Acute myeloid leukemia: A comprehensive review and 2016 update","volume":"6","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1080\/14656566.2016.1258056","article-title":"Efficacy of Azacitidine in the treatment of adult patients aged 65 years or older with AML","volume":"17","author":"Tenti","year":"2016","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/cas.13168","article-title":"Epigenetics in normal and malignant hematopoiesis: An overview and update 2017","volume":"108","author":"Goyama","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fonc.2015.00108","article-title":"The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis","volume":"5","author":"Sun","year":"2015","journal-title":"Front Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Chronic Myeloid Disorders Working Group of the International Cancer Genome, C. Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/leu.2013.336","article-title":"Landscape of genetic lesions in 944 patients with myelodysplastic syndromes","volume":"28","author":"Haferlach","year":"2014","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med., 368, 2059\u20132074.","DOI":"10.1056\/NEJMoa1301689"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/ajh.25104","article-title":"Chronic myelomonocytic leukemia: 2018 update on diagnosis, risk stratification and management","volume":"93","author":"Patnaik","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/17474086.2017.1380515","article-title":"Mutations in myeloproliferative neoplasms-their significance and clinical use","volume":"10","author":"Schischlik","year":"2017","journal-title":"Expert Rev. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1182\/blood-2013-04-496448","article-title":"Comprehensive mutational profiling in advanced systemic mastocytosis","volume":"122","author":"Schwaab","year":"2013","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nrc3343","article-title":"The role of mutations in epigenetic regulators in myeloid malignancies","volume":"12","author":"Shih","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/leu.2013.343","article-title":"Epigenetics of myelodysplastic syndromes","volume":"28","author":"Itzykson","year":"2014","journal-title":"Leukemia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrd4360","article-title":"Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders","volume":"13","author":"Falkenberg","year":"2014","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bcp.2017.09.007","article-title":"How to effectively treat acute leukemia patients bearing MLL-rearrangements?","volume":"147","author":"Steinhilber","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s13318-017-0404-3","article-title":"Preclinical Pharmacokinetics and Pharmacodynamics of Pinometostat (EPZ-5676), a First-in-Class, Small Molecule S-Adenosyl Methionine Competitive Inhibitor of DOT1L","volume":"42","author":"Waters","year":"2017","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1177\/2040620715576662","article-title":"Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: Emerging preclinical and clinical evidence","volume":"6","author":"Chaidos","year":"2015","journal-title":"Ther. Adv. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1586\/era.10.62","article-title":"Nonhistone protein acetylation as cancer therapy targets","volume":"10","author":"Singh","year":"2010","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41586-018-0387-5","article-title":"Inhibitors of histone acetyltransferases KAT6A\/B induce senescence and arrest tumour growth","volume":"560","author":"Baell","year":"2018","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ajh.22257","article-title":"Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies","volume":"87","author":"Puda","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1182\/blood-2012-02-413187","article-title":"Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes","volume":"123","author":"Pattabiraman","year":"2014","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.stem.2015.08.004","article-title":"HDAC8 Inhibition Specifically Targets Inv (16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation","volume":"17","author":"Qi","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/bjc.2016.36","article-title":"Inhibition of histone deacetylases in cancer therapy: Lessons from leukaemia","volume":"114","author":"Ceccacci","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.3109\/10428194.2015.1034705","article-title":"Analysis of class I and II histone deacetylase gene expression in human leukemia","volume":"56","author":"Yang","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1080\/10428190802527699","article-title":"Enhanced histone deacetylase enzyme activity in primary myelofibrosis","volume":"49","author":"Wang","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jmb.2004.02.006","article-title":"Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis","volume":"338","author":"Gregoretti","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1111\/febs.13746","article-title":"How do tumor cells respond to HDAC inhibition?","volume":"283","author":"Newbold","year":"2016","journal-title":"FEBS J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1007\/s00018-014-1656-6","article-title":"Histone deacetylase inhibitors and cell death","volume":"71","author":"Zhang","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nm1160","article-title":"Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway","volume":"11","author":"Insinga","year":"2005","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"723","DOI":"10.2217\/epi.10.59","article-title":"Histone deacetylase inhibitors in the therapy of cancer: Much to learn","volume":"2","author":"Lee","year":"2010","journal-title":"Epigenomics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nm1161","article-title":"Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells","volume":"11","author":"Nebbioso","year":"2005","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/sj.leu.2401508","article-title":"Histone deacetylase inhibitors are the potent inducer\/enhancer of differentiation in acute myeloid leukemia: A new approach to anti-leukemia therapy","volume":"13","author":"Kosugi","year":"1999","journal-title":"Leukemia"},{"key":"ref_47","first-page":"2766","article-title":"Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells","volume":"59","author":"Wang","year":"1999","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14639","DOI":"10.1073\/pnas.1008522107","article-title":"Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair","volume":"107","author":"Lee","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","first-page":"855","article-title":"Valproic acid sensitizes K562 erythroleukemia cells to TRAIL\/Apo2L-induced apoptosis","volume":"28","author":"Iacomino","year":"2008","journal-title":"Anticancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Silva, G., Cardoso, B.A., Belo, H., and Almeida, A.M. (2013). Vorinostat induces apoptosis and differentiation in myeloid malignancies: Genetic and molecular mechanisms. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053766"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/leu.2012.366","article-title":"HDAC inhibition by SNDX-275 (Entinostat) restores expression of silenced leukemia-associated transcription factors Nur77 and Nor1 and of key pro-apoptotic proteins in AML","volume":"27","author":"Zhou","year":"2013","journal-title":"Leukemia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1124\/jpet.106.118406","article-title":"Targeting AML1\/ETO-histone deacetylase repressor complex: A novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1\/ETO-positive acute myeloid leukemia cells","volume":"321","author":"Liu","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1182\/blood-2011-02-336743","article-title":"Efficacy of vorinostat in a murine model of polycythemia vera","volume":"119","author":"Akada","year":"2012","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5024","DOI":"10.1182\/blood-2009-05-222133","article-title":"Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells","volume":"114","author":"Wang","year":"2009","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1182\/blood-2009-07-231985","article-title":"AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit","volume":"115","author":"Lin","year":"2010","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9647","DOI":"10.18632\/oncotarget.14181","article-title":"Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis","volume":"8","author":"Lyberg","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/leu.2017.183","article-title":"SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis","volume":"32","author":"Martinelli","year":"2018","journal-title":"Leukemia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/5047","article-title":"Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer","volume":"21","author":"Cameron","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3892\/ijo.2014.2555","article-title":"Mechanisms and potential molecular markers of early response to combination epigenetic therapy in patients with myeloid malignancies","volume":"45","author":"Liu","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0145-2126(02)00222-9","article-title":"Preclinical evaluation of antineoplastic activity of inhibitors of DNA methylation (5-aza-2\u2032-deoxycytidine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemic cells","volume":"27","author":"Shaker","year":"2003","journal-title":"Leuk. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4161\/cbt.8.10.8213","article-title":"Panobinostat treatment depletes EZH2 and DNMT1 levels and enhances decitabine mediated de-repression of JunB and loss of survival of human acute leukemia cells","volume":"8","author":"Fiskus","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1038\/bcj.2013.68","article-title":"Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome","volume":"4","author":"Tan","year":"2014","journal-title":"Blood Cancer J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1080\/13543784.2016.1216971","article-title":"Panobinostat for the treatment of acute myelogenous leukemia","volume":"25","author":"Morabito","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1517\/13543784.2016.1146251","article-title":"Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes","volume":"25","author":"Stahl","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/bjh.13016","article-title":"A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome","volume":"167","author":"Kirschbaum","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12185-017-2327-9","article-title":"Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia","volume":"107","author":"Kobayashi","year":"2018","journal-title":"Int. J. Hematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.leukres.2018.06.007","article-title":"Addition of histone deacetylase inhibitors does not improve prognosis in patients with myelodysplastic syndrome and acute myeloid leukemia compared with hypomethylating agents alone: A systematic review and meta-analysis of seven prospective cohort studies","volume":"71","author":"Pan","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/cncr.29085","article-title":"Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia","volume":"121","author":"Issa","year":"2015","journal-title":"Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1200\/JCO.2015.66.2510","article-title":"Randomized Phase II Study of Azacitidine Alone or in Combination with Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117","volume":"35","author":"Sekeres","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1038\/leu.2017.159","article-title":"A phase 1b\/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with 30% blasts","volume":"31","author":"Sekeres","year":"2017","journal-title":"Leukemia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/cncr.30533","article-title":"Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated, higher-risk myelodysplastic syndromes","volume":"123","author":"Berdeja","year":"2017","journal-title":"Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1200\/JCO.2013.50.3102","article-title":"Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: Results of the US Leukemia Intergroup trial E1905","volume":"32","author":"Prebet","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/bjh.13832","article-title":"Eastern Cooperative Oncology G, North American Leukemia i: Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm: Further results of the E1905 North American Leukemia Intergroup study","volume":"172","author":"Prebet","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/leu.2016.282","article-title":"Dynamic changes in the clonal structure of MDS and AML in response to epigenetic therapy","volume":"31","author":"Uy","year":"2017","journal-title":"Leukemia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1868-7083-5-12","article-title":"Histone deacetylase inhibition in the treatment of acute myeloid leukemia: The effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents","volume":"5","author":"Fredly","year":"2013","journal-title":"Clin. Epigenetics"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Grishina, O., Schmoor, C., Dohner, K., Hackanson, B., Lubrich, B., May, A.M., Cieslik, C., Muller, M.J., and Lubbert, M. (2015). DECIDER: Prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1432-5"},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/bjh.12416","article-title":"A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia","volume":"162","author":"Andersen","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1365-2141.2010.08266.x","article-title":"A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms","volume":"150","author":"Rambaldi","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_81","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_82","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":"2017","journal-title":"Leuk. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1080\/10428194.2016.1228927","article-title":"Hypomethylating agent combination strategies in myelodysplastic syndromes: Hopes and shortcomings","volume":"58","author":"Ball","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/978-1-4419-9967-2_13","article-title":"Epigenetic therapies in MDS and AML","volume":"754","author":"Griffiths","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/cncr.30532","article-title":"Hypomethylating agents in combination with histone deacetylase inhibitors in higher risk myelodysplastic syndromes: Is there a light at the end of the tunnel?","volume":"123","author":"Stahl","year":"2017","journal-title":"Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:24:36Z","timestamp":1760196276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,9]]},"references-count":85,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19103091"],"URL":"https:\/\/doi.org\/10.3390\/ijms19103091","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,9]]}}}