Development of a new therapeutic strategy for the treatment of MLL-rearranged acute leukemia

Mixed lineage leukemia-rearranged (MLL-r) leukemia is a genetically distinct subtype of leukemia characterized by chromosomal translocations in the MLL1 gene KMT2A and associated with a poor prognosis. To obtain a better clinical outcome, multiple efforts are performed to explore treatment options that specifically target key players in the MLL-r mechanism. One such target is the lens epithelium derived growth factor, isoform p75 (LEDGF/p75). LEDGF/p75 serves as tether for the MLL1 complex to MLL1 target genes. In my thesis, we investigate the role of the LEDGF/p75 paralog HRP-2 in normal hematopoiesis and leukemogenesis. We study the interaction between HRP-2 and MLL1 in vitro. The role of HRP-2 in leukemogenesis was investigated using various leukemic cell lines and a systemic HRP-2 knockout mouse model. In a second part of this project, we study the potential to target LEDGF/p75 for treatment of mixed lineage leukemia.

Jaar van publicatie:2022

Toegankelijkheid:Open