RUXOLITINIB, A KINASE INHIBITOR, INHIBITS JANUS ASSOCIATED KINASES (JAKS) JAK1 AND JAK2 WHICH MEDIATE THE SIGNALING OF A NUMBER OF CYTOKINES AND GROWTH FACTORS THAT ARE IMPORTANT FOR HEMATOPOIESIS AND IMMUNE FUNCTION. JAK SIGNALING INVOLVES RECRUITMENT OF STATS (SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION) TO CYTOKINE RECEPTORS, ACTIVATION AND SUBSEQUENT LOCALIZATION OF STATS TO THE NUCLEUS LEADING TO MODULATION OF GENE EXPRESSION.
MYELOFIBROSIS (MF) AND POLYCYTHEMIA VERA (PV) ARE MYELOPROLIFERATIVE NEOPLASMS (MPN) KNOWN TO BE ASSOCIATED WITH DYSREGULATED JAK1 AND JAK2 SIGNALING. IN A MOUSE MODEL OF JAK2V617F-POSITIVE MPN, ORAL ADMINISTRATION OF RUXOLITINIB PREVENTED SPLENOMEGALY, PREFERENTIALLY DECREASED JAK2V617F MUTANT CELLS IN THE SPLEEN AND DECREASED CIRCULATING INFLAMMATORY CYTOKINES (EG, TNF-?, IL-6).