Saturday, May 7, 2022 10:00 AM – 10:45 AM ET Exhibit Hall, Workshop Room 2
Exhibitor Workshop: Sony Biotech., Inc.
Epigenetic Modulation of Leukemia Driver Mutation
- Jane Xu, Ph.D., Postdoctoral Fellow, Columbia Stem Cell Initiative, Columbia Univ., NY
A growing understanding of the molecular mechanisms underlying various cancers has contributed significantly to the evolution of cancer diagnostics and treatment. In leukemia, genetic mutations are thought to be the main driver of cellular transformation. However, leukemia cells harboring the same mutation or mutation clusters can actively remodel the epigenome and present divergent responses to ‘targeted’ therapy. Prior work demonstrated the establishment of determinants of clonal fitness within the leukemic epigenome in the absence of epigenetic mutations. It is still unknown how leukemia mutations modulate the epigenome and how this non-somatic influence underpins the functional and therapeutic heterogeneity. Our research focus is on elucidating the interactions between Stag2, the most frequently mutated cohesin member in cancer, and two leukemia driver mutations, Npm1c or Flt3-ITD. We hypothesize that cohesin dysfunction contributes to the establishment of the leukemic epigenome, which is vulnerable to genetic intervention. Determining the mechanistic interaction between the cohesin complex and Npm1c or Flt3-ITD may uncover novel pathophysiologic consequences of epigenetic alterations, and the relationship to therapeutic response divergency.