Pre-clinical evaluation of the hypomethylating agent decitabine for the treatment of t-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL

Young GI Societies in Europe: 2019 update

Abstract Background: One of the aims of the Young Talent Group (YTG) is to make United European Gastroenterology (UEG) more attractive to young fellows interested in gastroenterology (GI), and to actively involve them in UEG activities and the activities of their respective national societies. In 2017, we conducted a survey among the Friends of the UEG YTG with the aim of identifying the state of organization and needs of Young GI Sections (YGISs) throughout Europe, highlighting areas for further development and improvement. Aims: The aim of the current web-based survey was to assess the progress of YGISs over 1 year, and persisting hurdles in forming and running a YGIS. Results: Overall, 38 of 42 Friends answered the survey (91%). The number of YGISs has increased significantly from 12 in 2017 to 25 in 2019. Young gastroenterologists remained supported, but not influenced, by national societies. Results of the survey suggest that a lack of dedicated and motivated fellows has replaced a lack of funding as the most prevalent hurdle in forming these types of sections. Conclusion: Our survey shows that the development of YGISs has improved markedly within the last 2 years. However, several limitations, like underrepresentation in subcommittees of national societies, remain and need to be addressed in order to involve young gastroenterologists in their respective national societies and within UEG, to pave the way for future research, education and excellent quality of care, and reduce health inequalities across Europe