Medical and health sciences
- Analysis of next-generation sequence data
- Transcription and translation
PSIP1 was recently identified as an oncogene in KMT2A-rearranged leukemia and proposed as an interesting therapeutic target because of its dispensability in state-state hematopoiesis. However, in the context of T-cell acute lymphoblastic leukemia, our preliminary data indicate that PSIP1 may exert a dual role either as a tumor suppressor in disease initiation or as an oncogene in tumor maintenance, which warrants further functional studies on the dual role of PSIP1. The main goal of this fellowship application is to further investigate these divergent roles of PSIP1 in T-ALL and to unravel the downstream molecular mechanisms behind this duality. As such, we aim to identify downstream pathways or vulnerabilities that may ultimately lead to the development of novel, less toxic, anti-leukemic therapeutic strategies. In addition, it is important to know the putative side-effects associated with targeting the functions of PSIP1 to treat MLL-rearranged leukemia patients.