Erin Gourley Reid, MD
2010-12-05
“Stones,” “meth,” and polycomb group (PcG) protein take center stage rocking the lymphoid world in the scientific session titled “Epigenetic Regulation in Lymphoid Malignancies” taking place today at 7:30 a.m. in Hall F5; this session also took place yesterday morning. Don’t be fooled by the featured topics; this scientific session chaired by Dr. Wyndham Wilson boasts some serious translational science.
The field of epigenetics has exploded onto the scene over the last decade, rehabilitating the scientific community from addictions to models depicting genetic alterations as limited to the primary DNA sequence. During this time, histone acetylation, DNA methylation, and PcG transcriptional repression have been garnering increased appreciation for their roles in oncogenesis. Hematology has been a prominent venue for the elucidation of epigenetic mechanism, with myelodysplastic syndrome and lymphoma being the first to boast FDA-approved epigenetic modulators (5-azacitadine, dacitabine, and romidepsin, respectively).
Headlining, Dr. Steven Baylin explores themes common to embryonic and cancer stem cells, from DNA-methylation variations to histone modulations. Highlighting observations that silencing of genes is as important as oncogene activation in lymphoma, Dr. Baylin will elaborate on the emerging concept of a molecular progression of gene silencing during tumorigenesis that begins with initial PcG transcriptional repression.
Following Dr. Baylin, Dr. Kapil N. Bhalla adds microRNAs (MiRs) to the mix and reviews the complex interplay of the different epigenetic mechanisms at work in lymphoid malignancies. Epigenetic mechanisms he explores include histone modifications, DNA methylation, nucleosome remodeling, and small non-coding RNAs. While discussing therapeutic strategies, Dr. Bhalla stresses the importance of targeting the deregulated mechanisms in a combinatorial fashion.
Dr. Susan E. Bates wraps up the session with a review of approved and emerging epigenetic therapies highlighting their potential to reset the oncogenic phenotype. The gene alterations critical for clinical activity of these therapies are largely unknown, but Dr. Bates will discuss examples under investigation including several genes known to be hypermethylated in myelodyplastic syndrome, including the p15INK4B and the fragile histidine triad (FHIT) genes. She also presents data supporting that mechanisms of action of these ages may reach beyond the nucleus: multiple cellular proteins are also affected by acetylation, some of them potentially responsible for the activity of the HDAC inhibitors in lymphomas.
Each of the presenters highlight the need for further scientific effort to identify mechanisms of action and harmonious combinations of epigenetic therapies with each other as well as other non-epigenetic therapies. While this session focuses on lymphoma, the epigenetic principles presented here are relevant to a growing number of hematologic disorders and will prepare you for a variety of upcoming educational, scientific, and abstract sessions.
Dr. Reid receives research funding from Millennium for an investigator-initiated study and is a PI for pharma-sponsored trials from BMS, Millennium, and Novartis.
