Table 1.
JAK-Related Disorders and JAK Inhibitors.*.
| JAK | Activating Cytokines | Disorders Caused by Loss-of-Function Mutations | Disorders Caused by Gain-of-Function (Activating) Mutations | Pharmacologic Inhibitors |
|---|---|---|---|---|
| JAK1 | Common γ-chain cytokines; interleukin-6 family; interleukins 10, 13, and 22; granulocyte colony-stimulating factor; interferons α, β, and γ | T-cell acute lymphocytic leukemia, B-cell acute lymphocytic leukemia, acute myeloid leukemia, ABC diffuse large-B-cell lymphoma, acute myeloid leukemia with severe congenital neutropenia | Ruxolitinib, baricitinib, tofacitinib, GLPG0634, ASP015K, AZD1480 | |
| JAK2 | Erythropoietin and other hormonelike cytokines; interleukin-3 family; interleukin-6 family; interleukins 12 and 23; interleukin-13; granulocyte colony-stimulating factor; interferon-γ | Myeloproliferative neoplasm, polycythemia vera, essential thrombocythemia, primary myelofibrosis, Down’s syndrome–associated B-cell acute lymphoblastic leukemia, B-cell acute lymphocytic leukemia, primary mediastinal B-cell lymphoma, Hodgkin’s lymphoma | Ruxolitinib, baricitinib, tofacitinib, pacritinib, lestaurtinib, AZD1480 | |
| JAK3 | Common γ-chain cytokines | SCID | T-cell acute lymphocytic leukemia, adult T-cell leukemia–lymphoma, natural-killer T-cell lymphoma | Tofacitinib, VX-509, ASP015K |
| TYK2 | Interferons α and β; interleukins 6, 10, and 13; granulocyte colony-stimulating factor; interleukins 12 and 23 | Primary immunodeficiency |
*
The hormonelike cytokines include growth hormone, prolactin, thrombopoietin, and leptin. The interleukin-3 family comprises cytokines that use the common β subunit, including interleukins 3 and 5 and granulocyte colony-stimulating factor. The interleukin-6 family comprises cytokines that use glycoprotein 130, including interleukins 6, 11, and 27; oncostatin M; ciliary neurotrophic factor; cardiotrophin-1; and leptin. Cytokines that use the common γ chain include interleukins 2, 4, 7, 9, 15, and 21. ABC denotes activated B-cell-like, JAK Janus kinase, and SCID severe combined immune deficiency.