Description:
Dysregulation of epigenetic processes and chromatin programs are increasingly recognized as hallmarks of cancer and pre-cancerous clonal selection. Epigenetic dysregulation may occur due to ‘non-mutational epigenetic reprogramming’ involving epigenetic alterations independent of specific gene mutations, as well as mutation(s) in epigenetic regulatory genes. While these changes have been well described in normal and malignant hematopoietic processes and disorders, a major challenge in this field has been to functionally demonstrate causal relationships for the development of targeted therapies. This session will highlight recent cutting-edge research defining specific epigenetic and chromatin mechanisms that cause hematopoietic stem cell (HSC) selection, clonal diversification, and progression of hematologic malignancies. 

Dr. Gariella Ficz will present on the development and use of epigenetic editing to define causality between aberrant DNA hypermethylation and physiological changes in primary human HSCs and acute myeloid leukemia. Dr. Ficz will discuss implications of these data for our understanding of the biology of aging and pre-cancerous conditions. 

Dr. Cristina Pina will present identification of histone acetylation and Polycomb activity as critical elements in stabilizing transcriptional and cellular identity during pre-leukemia progression and leukemia initiation. Dr. Pina will discuss transcriptional noise, noise regulation by histone-modifying complexes, and the role of transcriptional noise in clonal diversification. 

Dr. Elisa Oricchio will present identification of histone acetylation as a critical regulator of 3D chromatin structure that is essential for oncogene expression and maintenance of lymphoma. Dr. Oricchio will discuss modulation of 3D chromatin structure by targeting epigenetic modifications to prevent the formation of oncogenic chromatin interactions.