Aspects biologiques de la voie JAK/STAT dans les néoplasmes myéloprolifératifs classiques négatifs pour BCR-ABL

Myeloproliferative disorders more recently named Myeloproliferative neoplasms (MPN) display several clinical entities: chronic myeloid leukemia (CML), the classical MPN including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and atypical and unclassifiable NMP. The term MPN is mostly used for classical BCR-ABL-negative (myeloproliferative disorder) (ET, PV, PMF). These are clonal diseases resulting from the transformation of an hematopoietic stem cell and leading to an abnormal production of myeloid cells. The genetic defects responsible for the myeloproliferative abnormalities are called « driver » mutations and all result in deregulation of the cytokine receptor / JAK2 / STAT axis. Among them, JAK2, the thrombopoietin receptor (MPL) and calreticulin (CALR) mutations are found in around 90% of the cases. These driver MPN mutations can be associated with other driver mutations also found in other hematological malignancies, especially in PMFs. These are chronic diseases with major risks being thrombosis, hemorrhage and cytopenias for PMF and the long-term progression to myelofibrosis and the transformation to leukemia. Most recent therapeutic have focused on targeting the JAK2 signaling pathway directly by inhibitors of JAK2 or indirectly. Interferon a allows in some cases hematologic and molecular remission patients.