Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML.
The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered. Citation: Leonard SM, Perry T, Woodman CB, Kearns P (2014) Sequential Treatment with Cytarabine and Decitabine Has an Increased Anti-Leukemia Effect Compared to Cytarabine Alone in Xenograft Models of Childhood Acute Myeloid Leukemia. PLoS ONE 9(1): e87475. doi:10.1371/journal.pone.0087475 Editor: Javier S. Castresana, University of Navarra, Spain Received November 13, 2013; Accepted December 26, 2013; Published January 28, 2014 Copyright: 2014 Leonard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Leukemia and Lymphoma Research UK and by Janssen Research and Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: This study was partly supported by Janssen Research and Development. Professor Pamela Kearns has undertaken consultancy work for Janssen Pharmaceuticals. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. * E-mail: email@example.com (CW); firstname.lastname@example.org (PK)