Swiss Society of Medical Oncology/Swiss Society of Hematology award for the best abstract presented at the Swiss Oncology Hematology Congress 2025 in the field of experimental hematology/oncology

Loss of SHP2 reduces JAK2V617F hematopoietic stem cell clone size and corrects MPN phenotype in preclinical models and patient cells
C. Albrecht, S. Arunasalam, S. Hallenberger-Jungius, S. Mattei, M. Christen, A. Rovo, A. Angelillo-Scherrer, S. Dirnhofer, B. G. Neel, R. L. Levine, R. Koche, S. C. Meyer
Presented by: S. Arunasalam

Myeloproliferative neoplasms (MPNs) are driven by constitutive JAK2 signaling, with persistent MAPK activation limiting the disease-modifying effects of JAK2 inhibitors. This study investigated the role of SHP2, a key MAPK mediator, in sustaining malignant signaling and clonal persistence. Genetic depletion or pharmacologic inhibition of SHP2 suppressed MAPK signaling, sensitized JAK2V617F cells to ruxolitinib, and reduced malignant clone size in vitro and in mouse models. In competitive transplantation assays, SHP2 loss significantly decreased JAK2V617F stem/progenitor cell burden. Combined SHP2 and JAK2 inhibition produced the most robust correction of cytosis, splenomegaly, and progenitor expansion in multiple MPN models and in primary patient cells. These findings identify SHP2 as a critical driver of MPN persistence and support combined SHP2/JAK2 inhibition as a promising disease-modifying therapeutic strategy.

https://www.sohc.ch/abstract/awards-2025/