Janus Kinase Deregulation in Leukemia and Lymphoma Edwin Chen, Louis M. Staudt, Anthony R. Green  Immunity  Volume 36, Issue 4, Pages 529-541 (April 2012) DOI: 10.1016/j.immuni.2012.03.017 Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 1 Summary of JAK Mutations Discovered in Hematological Malignancies Color-coded representation of the location of each mutant residue within the domain structure of each JAK protein. The majority of mutations in JAK proteins are found within the pseudokinase or kinase domain. Immunity 2012 36, 529-541DOI: (10.1016/j.immuni.2012.03.017) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 2 Signaling Complexities of Janus Kinases Janus kinases (JAKs) such as JAK2 can modulate signaling through multiple different cytokine receptor families, and can activate multiple downstream canonical pathways such as STATs, PI3K and ERK, as well as non-canonical pathways via direct nuclear targeting. The biological consequences elicited by oncogenic JAK signaling will therefore depend on the complement of receptors, STATs and other signaling pathway components present in that cellular context. Immunity 2012 36, 529-541DOI: (10.1016/j.immuni.2012.03.017) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 3 JAK-STAT Signaling in Lymphomas Top: Autocrine JAK-STAT3 signaling in activated B cell like diffuse large B cell lymphoma. MYD88 mutants activate NF-κB and p38 MAP kinase signaling pathways to increase production and secretion of IL-6 and IL-10, which in turn activate the JAK-STAT3 pathway by autocrine stimulation of their respective receptors. MYD88 mutants can also activate type I interferon pathways through increased production of IFN-β. Bottom, Molecular consequences of 9p24 amplification in Hodgkin lymphoma and primary mediastinal B cell lymphoma. Increased expression of JAK2 and JMJD2C following 9p24 amplification synergizes to destabilize heterochromatic state and positively regulate expression of multiple genes (such as those encoding MYC, JAK2, JMJD2C, IL4RA, PD-L1, and PD-L2) that promote increased growth factor signaling, immune suppression and proliferation. Immunity 2012 36, 529-541DOI: (10.1016/j.immuni.2012.03.017) Copyright © 2012 Elsevier Inc. Terms and Conditions