Presentation Title
Unraveling the Role of AF10 in Acute Leukemia
Abstract
Non-random chromosomal translocations represent a common cytogenetic abnormality in acute leukemia, and understanding the functional alterations of these translocations is critical for developing effective treatment for patients. Mixed Lineage Leukemia Translocated to 10 (AF10) is found translocated in-frame with up to seven different genes, all leading to the development of acute myeloid or acute lymphoid leukemia (AML or ALL). While the role of AF10 is broadly known to be a cofactor of the histone methyltransferase, DOT1L, the extent of its function in leukemia remains understudied. As previously shown in colorectal cancer cells, AF10 directly interacts with b-catenin and is required for proper Wnt/b-catenin target gene expression. Activation of the canonical Wnt/b-catenin pathway, normally inactivated after hematopoietic differentiation, is critical for the development of myeloid and lymphoid leukemic stem cells. It is not known how perturbed AF10 alters the Wnt transcriptional response in leukemia cells, but uncovering these consequences is vital for a better understanding of the mechanisms driving AF10 translocated leukemogenesis. We have confirmed the interaction of AF10 and b-catenin in leukemic cells, and will investigate the role of AF10 and AF10 fusion proteins in Wnt signaling in leukemia.
Primary Faculty Mentor Name
Jessica Heath
Faculty/Staff Collaborators
Jessica Heath
Status
Graduate
Student College
Larner College of Medicine
Program/Major
Cellular, Molecular and Biomedical Sciences
Primary Research Category
Biological Sciences
Secondary Research Category
Health Sciences
Unraveling the Role of AF10 in Acute Leukemia
Non-random chromosomal translocations represent a common cytogenetic abnormality in acute leukemia, and understanding the functional alterations of these translocations is critical for developing effective treatment for patients. Mixed Lineage Leukemia Translocated to 10 (AF10) is found translocated in-frame with up to seven different genes, all leading to the development of acute myeloid or acute lymphoid leukemia (AML or ALL). While the role of AF10 is broadly known to be a cofactor of the histone methyltransferase, DOT1L, the extent of its function in leukemia remains understudied. As previously shown in colorectal cancer cells, AF10 directly interacts with b-catenin and is required for proper Wnt/b-catenin target gene expression. Activation of the canonical Wnt/b-catenin pathway, normally inactivated after hematopoietic differentiation, is critical for the development of myeloid and lymphoid leukemic stem cells. It is not known how perturbed AF10 alters the Wnt transcriptional response in leukemia cells, but uncovering these consequences is vital for a better understanding of the mechanisms driving AF10 translocated leukemogenesis. We have confirmed the interaction of AF10 and b-catenin in leukemic cells, and will investigate the role of AF10 and AF10 fusion proteins in Wnt signaling in leukemia.