Myeloproliferative neoplasms (MPN) are chronic leukemias characterized by constitutive activation of JAK2 tyrosine kinase signaling. Clinical JAK2 inhibitors bring benefits for patients, but have limited disease-modifying activity. Allogeneic hematopoietic cell transplantation is the only curative treatment to date.
The Meyer lab has a specific interest in the oncogenic signaling driving MPN. We have demonstrated that activation of the MAPK pathway with MEK1/2 and ERK1/2 kinases, which is involved in several cancers, limits JAK2 inhibitor therapy and needs to be addressed to enhance efficacy (Stivala, JCI 2019; Brkic, Leukemia 2021). These findings have translated to a first clinical study (ADORE, NCT04097821). A phase 1/2a investigator initiated trial (IIT) on combined JAK2 and MEK inhibition in pre-transplant patients is currently being initiated at University Hospitals Bern (Inselspital) and Basel (USB).
Our lab is investigating mechanisms of resistance, which mediate loss of response to clinical JAK2 inhibitors, and approaches to overcome resistance (Meyer, Cancer Cell 2015; Codilupi, CCR 2024). We are studying primary MPN patient cells using multi-omics approaches, as well as transgenic mouse and cell-based models as well as an ex vivo bioreactor platform. Notably, we are involved in the characterization of novel types of JAK2 inhibitors incl. type II JAK2 inhibitors currently in development towards clinical studies (Usart, Meyer et al, Blood 2025).
