A novel therapeutic approach for acute leukemia by targeting LEDGF/p75.

Acute leukemia is a cancer characterized by rapid expansion of malignant white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Although current treatment regimens reach long-term survival rates of more than 80% in some types of leukemia, other types have a worse prognosis and a large portion of the patients will relapse. Therefore, new treatment strategies are needed to improve life expectancy and life quality of these patients. Acute leukemia is often characterized by chromosomal translocations involving the MLL gene (Mixed Lineage Leukemia), leading the formation of malignant fusion proteins. MLL, a protein involved in normal blood cell formation and regulation of gene expression, is part of a multi-protein complex, tethered to its target genes by LEDGF/p75 (Lens Epithelium Derived Growth Factor/p75) through a triple interaction with menin. In this project we validate of the MLL/menin-LEDGF/p75 interaction as a target to treat MLL mediated acute leukemia. We investigate the cellular function of LEDGF/p75 and the interaction with MLL/menin and initiate the search for small molecules blocking this interaction.

Keywords:Drug development, Menin, MLL, Leukemia, Cancer, LEDGF/p75

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences