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Six (or More) Drugs in Search of a Mechanism: DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes

Steven D. Gore

M Muggia FM . 5-Azacytidine. A new anti-cancer drug with effectiveness in acute myelogenous leukemia . Ann Intern Med 1976 ; 85 : 237 – 245 . 5. Momparler RL Bouchard J Onetto N . 5-aza-2′-deoxycytidine therapy in patients with acute

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Novel Biospecific Agents for the Treatment of Myelodysplastic Syndromes

Jason Gotlib and Peter L. Greenberg

Levels of treatment for patients with myelodysplastic syndromes (MDS) fall within 3 broad categories: supportive care, low- and high-intensity therapy. Most approaches remain experimental, and supportive care remains the standard of treatment in MDS. In parallel with the growing knowledge of the multiple pathobiologic abnormalities in MDS, increasing numbers of low-intensity, biospecific agents that target these pathogenetic lesions have entered clinical trial testing. Although the term “biospecific” has been applied to many of these investigational drugs, they often exert pleiotropic effects, many of which remain to be identified. An ongoing challenge will be to more fully characterize the mechanisms of action of these drugs and to characterize biologic correlates of response. With these data in hand, it will be increasingly feasible to treat patients with combinations of biospecific drugs with non-overlapping actions and toxicities, a therapeutic approach that is likely required to effectively overcome the barriers posed by the biologic heterogeneity of MDS. This review focuses on recent therapeutic approaches using such biologic response modifiers to treat MDS.

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Epigenetic Modulation in Hematologic Malignancies: Challenges and Progress

Constantine S. Mitsiades and Kenneth C. Anderson

. Ann Hematol 2009 ; 88 : 213 - 219 . 81. Maslak P Chanel S Camacho LH . Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic

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Acute Myeloid Leukemia

Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Steven E. Coutre, Lloyd E. Damon, James M. Foran, Salil Goorha, Lori J. Maness, Guido Marcucci, Peter Maslak, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, and Eunice S. Wang

-C therapy was associated with a higher complete remission rate (18% vs. 1%) and longer overall survival compared with hydroxyurea. Fenaux et al. 65 compared 5-azacytidine with conventional care (e.g., best supportive care, low-dose Ara-C, intensive

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Acute Myeloid Leukemia

Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Daniel A. Arber, Eyal Attar, Uma Borate, Steven E. Coutre, Lloyd E. Damon, Salil Goorha, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, Eunice S. Wang, Maoko Naganuma, and Kristina M. Gregory

inhibitors. An international randomized phase III study by Fenaux et al. 90 compared the hypomethylating agent 5-azacytidine with conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy) in patients with MDS (N = 358

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The Multifaceted Nature of Myelodysplastic Syndromes: Clinical, Molecular, and Biological Prognostic Features

Peter L. Greenberg

methylation. 62 Modification of this hypermethylation gene profile is being used therapeutically in treating patients with MDS with hypomethylating agents such as 5-azacytidine and decitabine, often with beneficial results. Methylation of CpG dinucleotides

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Blastic Plasmacytoid Dendritic Cell Neoplasm

Akriti Jain and Kendra Sweet

: E75 – 77 . 47. Laribi K , Denizon N , Ghnaya H , Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases treated by 5-azacytidine . Eur J Haematol 2014 ; 93 : 81 – 85 . 48. Khwaja R , Daly A

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Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology

Aaron T. Gerds, Jason Gotlib, Prithviraj Bose, Michael W. Deininger, Andrew Dunbar, Amro Elshoury, Tracy I. George, Ivana Gojo, Krishna Gundabolu, Elizabeth Hexner, Gabriela Hobbs, Tania Jain, Catriona Jamieson, Andrew T. Kuykendall, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Erik Ranheim, Lindsay Rein, Rachel Salit, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Pankit Vachhani, Martha Wadleigh, Katherine Walsh, Dawn C. Ward, Mary Anne Bergman, and Hema Sundar

, ponatinib) or hypomethylating agent (eg, 5-azacytidine) has been shown to be effective for MLN-Eo with FGFR1 rearrangement in single case reports 100 , 101 The role for TKI as maintenance therapy after allogeneic HCT has not been systematically evaluated

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Drug Development Pipeline for Myeloproliferative Neoplasms: Potential Future Impact on Guidelines and Management

Prithviraj Bose and Srdan Verstovsek

: 965 – 970 . 74. Daver NG Cortes JE Zhou L . Ruxolitinib (RUX) in combination with 5-azacytidine (AZA) as therapy for patients (pts) with myelofibrosis (MF) [abstract] . Haematologica 2015 ; 15 ( Suppl 2 ): Abstract 808 . 75

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Historical Views, Conventional Approaches, and Evolving Management Strategies for Myeloproliferative Neoplasms

Brady L. Stein, Jason Gotlib, Murat Arcasoy, Marie Huong Nguyen, Neil Shah, Alison Moliterno, Catriona Jamieson, Daniel A. Pollyea, Bart Scott, Martha Wadleigh, Ross Levine, Rami Komrokji, Rebecca Klisovic, Krishna Gundabolu, Patricia Kropf, Meir Wetzler, Stephen T. Oh, Raul Ribeiro, Rita Paschal, Sanjay Mohan, Nikolai Podoltsev, Josef Prchal, Moshe Talpaz, David Snyder, Srdan Verstovsek, and Ruben A. Mesa

combination when used concurrently, and relative safety of the latter, noting a sample size of 6 patients. 102 , 103 In accelerated MF or blast phase MPN, a novel approach involves the use of hypomethylating agents (decitabine or 5-azacytidine