The Investigation of mTOR, JAK

Introduction. BCR/ABL negative myeloproliferative neoplasms (MPN) include primary myelofibrosis, polycythaemia vera, essential thrombocythemia. It is known that MPN pathogenesis is very complicated and insufficiently analysed. Constitutively activated JAK/STAT signaling pathway is a common feature of the MPN, JAK2 inhibitors have been proven to be clinically efficacious. However, they are not mutation specific and competent enough to suppress neoplastic clonal hematopoiiesis. Therefore, there is a need for exploring new therapeutic strategies for MPN. A potential treatment target are alternative signaling systems, such as P13K/Akt/mTOR and Hedgehog that has been found to be activated in MPN cells. The aim. The aim of this pilot study was to characterize and compare the effects of specific JAK/STAT, P13K/Akt/mTOR and Hedgehog signaling inhibitors in hematological cell cultures. Material and methods. In this study we explored the potent effect of targeting JAK/STAT, P13K/Akt/mTOR and Hedgehog pathways with specific agents in vitro. We evaluated the effect of JAK1/2, mTOR and Gli1/Gli2 inhibitors. Experiments was carried out with JAK2 p.V617F mutated SET-2 and JAK2 wild-type UT-7 human cell lines.. [...].