Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT

• Published in: Frontiers in immunology Vol. 9; p. 631
• Main Authors: Bandara, Geethani, Muñoz-Cano, Rosa, Tobío, Araceli, Yin, Yuzhi, Komarow, Hirsh D, Desai, Avanti, Metcalfe, Dean D, Olivera, Ana
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.03.2018
• Subjects: Adamantane - analogs & derivatives; Adamantane - pharmacology; Animals; Apoptosis; Carcinogenesis; Cell Proliferation; Cell Survival; D816V; DNA Repair; Hematologic Neoplasms - genetics; Hematologic Neoplasms - metabolism; Humans; Hydrazines - pharmacology; Immunology; Mast Cells - physiology; mastocytosis; Mastocytosis - genetics; Mastocytosis - metabolism; Mice; Mice, Knockout; Mutation - genetics; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors; Phosphotransferases (Alcohol Group Acceptor) - genetics; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Protein Isoforms - antagonists & inhibitors; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Pyrazoles - pharmacology; Pyridines - pharmacology; sphingosine kinase; sphingosine kinase inhibitor; sphingosine-1-phosphate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; D816V; mastocytosis; sphingosine kinase; KIT; sphingosine-1-phosphate; mast cells; sphingosine kinase inhibitor

Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration...