Project Grant F31CA298737

ROLE OF GLYCOSYLATED RNAS IN ACUTE MYELOID LEUKEMIA - PROJECT SUMMARY/ABSTRACT ACUTE MYELOID LEUKEMIA (AML) IS A MALIGNANT BLOOD DISORDER CHARACTERIZED BY THE ACCUMULATION OF IMMATURE MYELOID PROGENITORS AT THE EXPENSE OF DIFFERENTIATED PROGENY. DESPITE THE GENETIC HETEROGENEITY OF AML AND CLINICAL TREATMENTS, THERE PERSISTS A COMMON FOCUS ON ENHANCING CLINICAL OUTCOMES AND IN COMPREHENDING THE SIGNALING MECHANISMS THAT ALLOW FOR AML MAINTENANCE. THE RECENT DISCOVERY GLYCOSYLATED RNAS (GLYCORNAS), RNA MOLECULES POST-TRANSCRIPTIONALLY MODIFIED WITH SIALYLATED-N GLYCANS, HAS UPENDED OUR TRADITIONAL UNDERSTANDING OF RNA BIOLOGY. COLLABORATOR DATA HAS DEMONSTRATED CELL SURFACE GLYCORNAS CAN SERVE AS A SIGNALING MECHANISM BETWEEN MYELOMONOCYTIC CELL TYPES. GIVEN THIS INFORMATION, THE GOAL FOR THIS PROPOSAL IS TO CHARACTERIZE AND DEFINE THE ROLE OF GLYCORNAS IN ACUTE MYELOID LEUKEMIA. THE FIRST AIM WILL CHARACTERIZE GLYCORNA EXPRESSION AND SEQUENCES IN DISTINCT AML SUBTYPES WITH THOSE FROM NORMAL MYELOID PROGENITORS. THE SECOND AIM WILL DEFINE THE ROLE OF SIDT PROTEINS IN AML GLYCORNA EXPRESSION AND THE THIRD AIM WILL DETERMINE THE FUNCTIONS OF GLYCORNAS IN AML BIOLOGY AS IT PERTAINS TO AML DEVELOPMENT IN VIVO, REGULATING LEUKEMIC CELL HOMING, AND MIGRATORY CAPACITY. SUCCESSFUL EXECUTION OF THESE AIMS WILL PROVIDE VALUABLE INSIGHT ON THE EXPRESSION, REGULATORY MECHANISM, AND FUNCTION OF GLYCORNAS IN AML. COMPLETION OF THIS WORK WILL PROVIDE SIGNIFICANT ADVANCEMENTS, POTENTIALLY LEADING TO NOVEL CLINICAL THERAPIES FOR AML.