Physiology and Biophysics
Weill Cornell Medicine
Lab Website: www.masonlab.net
Single-Cell Resolution of Leukemia’s Epigenetic Evolution during Therapy
The central dogma of molecular biology (DNA!RNA!protein) is the key framework for almost all organisms. Yet, this is an incomplete dogma, about which we are still learning key components. Specifically, since the same DNA is present in all the cells of a person’s body, other mechanisms must regulate how and when genes (portions of DNA) are turned on and off, which then guide the cells’ activities. Collectively, this is called the “epigenome,” which fine-tunes the activity of DNA in each cell and enables a single set of DNA instructions in the embryo to blossom into the trillions of specialized cells that comprise the human body.The importance of the epigenome is also evident in certain cancers, including acute myeloid leukemia (AML). Despite the widespread use of chemotherapy in AML, it remains a mostly fatal disease (50-55%). When patients relapse after initial therapy, they often develop chemo-resistant AML; yet in many cases the tumor shows no genetic differences. Instead, it is the epigenetic changes that are relapse-specific, and we have shown that they are associated with AML pathogenesis and relapse. We predict that adaptation and survival of AML cells occurs through the epigenome. We will use new computational and biochemical methods to define these epigenetic sub-types, which can further separate AML patients previously labeled as “intermediate”. This provides new methods to characterize the aggressiveness of a person’s cancer. Importantly, our findings may offer new therapeutic and diagnostic approaches that could improve the clinical outcomes in AML.