HiJAKing the epigenome in leukemia and lymphoma

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by receptors of diverse cytokines, growth factors, and other related molecules. Many of these receptors transmit anti-apoptosis, proliferation, and differentiation signals that are critical for normal hematopoiesis and immune response. However, the JAK/STAT signaling pathway is deregulated in many hematologic malignancies, and as such is co-opted by malignant cells to promote their survival and proliferation. It has recently come to light that an alternative mechanism, wherein nuclear JAKs epigenetically modify the chromatin to increase gene expression independent of STATs, also plays an important role in the pathogenesis of many hematologic malignancies. In this review, we will focus on common genetic alterations of the JAK family members in leukemia and lymphoma, and provide examples in which JAKs regulate gene expression by targeting the cancer epigenome.