This conversation features Claire Harrison, a haematologist with expertise in MPNs, Alex Rampotas, a clinician-researcher focused on CAR-T therapies, Jean-Jacques Kiladjian, a hematologist with a deep understanding of MPN biology, and John Mascarenhas, involved in MPN clinical trials. They explore the potential of targeting mutant CALR in MPNs. Key insights include the promising early results of the INCA33989 trial, the development of CAR-T therapies aimed at mutant CALR, and innovative approaches using organoid models to test immunotherapies effectively.