February 2018 - Georg Greiner

Dr. med. univ. Georg Greiner, PhD

MedUni Wien RESEARCHER OF THE MONTH, February 2018

Systemic mastocytosis (SM) is characterized by abnormal accumulation of neoplastic mast cells (MC) harboring the activating KIT mutation D816V. Furthermore, increased production of pro-fibrogenic and angiogenic cytokines and related alterations of the bone marrow are commonly found in SM. Thus, we screened for KIT D816V-dependent production of various cytokines relevant to inflammation and identified C-C motif chemokine ligand-2 (CCL-2) as highly upregulated. CCL-2 secreted by KIT D816V+ MC was found to promote the migration of human endothelial cells in vitro and enhanced neovascularization in a mouse model. Finally, CCL-2 serum concentrations were found the be significantly elevated in mastocytosis patients compared to controls. In summary, we have identified CCL-2 as a novel key regulator of vascular cell migration and angiogenesis contributing to pathogenesis in SM.

Selected Literature

1. Valent, P., C. Akin, and D.D. Metcalfe, Mastocytosis 2016: Updated WHO
   Classification and Novel Emerging Treatment Concepts. Blood, 2016.
2. Greiner, G., et al., Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis. Clin Chem, 2017.
3. Horny, H.P. and P. Valent, Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. Leuk Res, 2001. 25(7): p. 543-51.
4. Hoermann, G., Greiner G., and Valent P., Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms. Mediators Inflamm, 2015. 2015: p. 869242.
5. Greiner, G., et al., CCL2 is a KIT D816V-dependent modulator of the bone marrow microenvironment in systemic mastocytosis. Blood, 2017. 129(3): p. 371-382.