A Novel Compound for Targeted Treatment of Core Binding Factor Leukemia

Core binding factor (CBF) leukemia is a rare cancer with a survival rate of less than 50 percent. Standard treatments are nonspecific chemotherapy and bone marrow transplantation, which are frequently associated with significant side effects, including life-threatening infections, bleeding, kidney dysfunction and even death. This project aims to develop a drug targeted to the specific genetic abnormality responsible for CBF leukemia that can significantly improve survival with fewer complications than current treatments.

Scientific Synopsis

Leukemia is a bone marrow cancer involving developing white blood cells and often is associated with specific, recurrent chromosome translocations and inversions that generate fusion genes, which play critical roles in leukemogenesis.

In this project, targeted treatments are being developed for a subgroup of leukemia based on current understanding of how leukemia develops at the molecular level. The “CBF” subgroup of leukemia contains CBF fusion genes that have been shown to play critical roles in leukemia development. Current treatments for CBF leukemia are not optimal, with long-term survival at 50 percent. The research team conducted a small chemical library screen to find inhibitors that block CBF protein interactions. Through biochemical, cell culture and animal model studies, they identified three chemically related lead compounds. In particular, one of the three compounds has shown leukemia reduction capability similar to standard chemotherapy drugs in preliminary studies in a mouse CBF leukemia model. The researchers will complete efficacy studies in this mouse model, develop one or more backup compounds, optimize formulation, and perform pharmacokinetics and toxicology tests that will lead to clinical trials.

Lead Collaborator

National Human Genome Research Institute, Bethesda, Maryland

Paul Liu, M.D., Ph.D.

Public Health Impact

Currently, the long-term survival rate for CBF AML is about 50 percent. Moreover, current standard care, chemotherapy and bone marrow transplantation, frequently are associated with significant side effects. The target-specific drug this project is developing may lead to significant improvement in the overall survival rate and reduce treatment-associated complications for CBF leukemias.


TRND researchers successfully optimized and demonstrated the utility of the animal disease model and showed for the first time that the initial lead compound is effective in the models as a monotherapy. TRND researchers assessed the tolerability of the lead compound in the mouse, resulting in a decision to discontinue its further development. Subsequently, the collaborator developed an improved in vitro efficacy assay, using cells extracted from bone marrow, to support the medicinal chemistry. Currently, a new the lead compound with significantly improved pharmacokinetics and tolerability after repeat dosing in mice is being evaluated in the mouse model.