Ruxolitinib, a JAK 1/JAK 2 kinase inhibitor, was recently approved by the Food and Drug Administration for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. JAK kinases mediate signaling of cytokines and growth factors that are involved in hematopoiesis and immune function. JAK signaling involves the recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, STAT activation, and localization of STATs to the nucleus, which results in the modulation of gene expression. Myelofibrosis is associated with aberrant JAK signaling. Ruxolitinib acts to attenuate downstream signaling by inhibiting JAK 1 and JAK 2 kinases, which results in reduced plasma cytokine levels and the induction of antiproliferative and proapoptotic effects...
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