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Editorials
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Tobío et al. suggest that signaling through these target molecules leads to IL-6 production in neoplastic mast cells (Figure 1).15 Finally, IL-6 effects can directly be blocked by applying antibodies against IL-6 or the IL-6 receptor.24 However, it remains unclear whether these drugs can block the symptoms and pathologies in patients with SM.
Acknowledgments and Funding
Research by PV and his team is supported by the Austrian Science Fund, grants F4701-B20 and F4704-B20.
References
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Figure 1. An overview of the con- cept proposed by Tobío et al.15 of the KIT D816V-dependent signal- ing machinery that involves PI3K, AKT, TOR, and JAK2-STAT5 and triggers IL-6 production in neo- plastic mast cells. In most patients with systemic mastocyto- sis, the transforming KIT mutation D816V is expressed in neoplastic mast cells. The KIT mutant form induces oncogenic signaling path- ways which in turn leads to an abnormal production of various effector molecules, including cytokines. One such cytokine is interleukin-6 (IL-6). In contrast to normal mast cells, KIT D816V- transformed mast cells express and release substantial amounts of this cytokine (red arrows). Once released, IL-6 acts as an autocrine growth stimulator as well as a trig- ger of cell activation and inflam- mation. The effects of IL-6 on vari- ous target cells are exerted via specific IL-6 receptors (IL-6R).
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