B02: Investigation into the plastic state of dormancy in JAK2-V617F driven myeloproliferative neoplasms (MPNs) and secondary acute myeloid leukemias (sAMLs)

Project B02 will analyze the JAK2-inhibitor-mediated modulation of the plastic state of dormancy during the transition of JAK2-V617F-driven Myeloproliferative Neoplasms (MPNs) into secondary myelofibrosis (sMF) and secondary acute myeloid leukemia (sAML). Using mouse models of Polycythemia Vera (PV), sMF and sAML, as well as patient-derived material and xenografts, B02 aims to explore whether dormancy within the mutant HSC compartment plays a biologically-relevant role in JAK2VF disease propagation, as well as in relapse after JAK2 inhibitor treatment. Perturbation of candidate genes regulating the state of dormancy will reveal novel therapeutic targets of dormant, JAK2-inhibitor resistant malignant cells.