Targeting Kindlin-3 in resistant MPNs

This project focuses on myeloproliferative neoplasms (MPNs), a group of blood disorders driven by genetic mutations causing abnormal growth of cells, particularly leukemic stem cells (LSCs), and how these cells modulate and interact with their bone marrow surroundings. This bidirectional interplay is thought to contribute to MPN progression and development of resistances to current treatments. We and others have shown that integrin adhesion molecules facilitate leukemic cell attachment to and mediate signaling from the tumor cell supporting environment. Here, we will specifically investigate the function of Kindlin-3, a protein required for full integrin function in blood cells, and its involvement in MPN disease development and progression. Together with the TARGET-MPN research group we aim to define cellular MPN niche integrin-ligand interactions and signaling pathways involved in Kindlin-3 regulation to develop treatment approaches mobilizing and targeting LSCs.