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Highly Specific JAK3 Inhibitors and the Future of T Cell Lymphoma Treatment

Wei Chen

Janus kinse-3 (JAK3) exclusively associates with common gamma chain (γc) receptor of γc-cytokines. When γc cytokines, such as IL-2, IL-15, IL-21, IL-4, IL-7 and IL-9, bind their receptors, JAK3, in combination with JAK1 and downstream signal transducers and activators of transcription, STATs, initiate critical signaling cascades. These pathways underlie the hematopoiesis, proliferation and differentiation of normal hematopoietic cells. Conversely, the aberrant, constitutive activation of the JAK-STAT signaling pathways, including JAK3’s, is associated with immune related disorders and cancers. Thus, inhibition of JAK-STAT signaling and their downstream tyrosine kinases have provided a therapeutic approach for treatment of several hemopoietic malignancies, especially T cell lymphomas. These cells typically harbor activating JAK mutations that lead to increased JAK-STAT signaling. In this review, we summarize the most recent developments of the JAK3 inhibitors on treatment of T cells lymphomas.