Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412

Highlights • KIT K509I germline mutation is associated with familial systemic mastocytosis. • Mastocytosis with KIT K509I mutation is sensitive to imatinib, dasatinib and PKC412. • Imatinib, dasatinib and PKC412 reduce P70S6K phosphorylation in KIT K509I cells. • Imatinib is more effective in induci...

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Veröffentlicht in:	Leukemia research 2014-10, Vol.38 (10), p.1245-1251
Hauptverfasser:	de Melo Campos, Paula, Machado-Neto, João A, Scopim-Ribeiro, Renata, Visconte, Valeria, Tabarroki, Ali, Duarte, Adriana S.S, Barra, Flávia F.C, Vassalo, José, Rogers, Heesun J, Lorand-Metze, Irene, Tiu, Ramon V, Costa, Fernando F, Olalla Saad, Sara T, Traina, Fabiola
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Apoptosis - drug effects Base Sequence Benzamides - pharmacology Blotting, Western Dasatinib Familial mastocytosis Female Germ-Line Mutation Hematology, Oncology and Palliative Medicine Humans Imatinib Imatinib Mesylate K509I KIT mutation Mastocytosis, Systemic - drug therapy Mastocytosis, Systemic - genetics Piperazines - pharmacology PKC412 Protein Kinase Inhibitors - therapeutic use Proto-Oncogene Proteins c-kit - genetics Pyrimidines - pharmacology Staurosporine - analogs & derivatives Staurosporine - pharmacology Thiazoles - pharmacology Tyrosine kinase inhibitors Young Adult
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Zusammenfassung:	Highlights • KIT K509I germline mutation is associated with familial systemic mastocytosis. • Mastocytosis with KIT K509I mutation is sensitive to imatinib, dasatinib and PKC412. • Imatinib, dasatinib and PKC412 reduce P70S6K phosphorylation in KIT K509I cells. • Imatinib is more effective in inducing apoptosis of neoplastic KIT K509I mast cells. • Imatinib induces good clinical response in KIT K509I familial mastocytosis.
ISSN:	0145-2126 1873-5835
DOI:	10.1016/j.leukres.2014.07.010