Exploring the Role of Mediator Complex Subunit 12-like (MED12L) in rare myeloid neoplasms

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2021

Our research focuses on the study of rare forms of myeloid neoplasms, blood diseases originating in the bone marrow. Among myeloid neoplasms, myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have somehow opposite characteristics: in MPN the bone marrow produces too many white blood cells, red blood cells or too many platelets, as in Essential Thrombocytemia (ET), while in MDS the bone marrow fails to generate enough cells, giving rise to anemia. Both can transform in leukemia, more difficult to cure. One of the forms of MDS, called MDS-RS-T, shares with ET some features such as the excess of platelets, likely due to a common defect in a gene called JAK2, and this increases the risk of thrombosis. With our study we aim at understanding if a molecule not studied before, called MED12L, plays a role in generating blood cells and especially platelets starting from the stem cells within the bone marrow, from which all blood cells are generated, and if it plays a role in MPN and MDS. From our previous studies we suspect that in a portion of patients there is an increased amount of MED12L in the bone marrow stem cells, likely due to the defect in JAK2. With our study we want to confirm this observation in a larger number of patients. In addition, by exploiting an experimental model of MPN, we want to understand if MED12L is responsible for the increased platelets production in MPN and MDS patients, and if we can control disease emergence or disease course by eliminating it. These rare myeloid neoplasms have unmet clinical needs: current therapies are aimed at controlling symptoms, improve quality of life and overall survival, and decrease progression to leukemia, however they do not provide a definitive cure. The final goal of our study is to discover new molecules that can be targeted with innovative drugs, or to find out molecules functioning as markers to promptly identify patients with more severe forms of the disease for a personalized cure.