title: Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412.
abstract: Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: de Melo Campos
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: João A
authors.initials: JA
authors.lastname: Machado-Neto
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Scopim-Ribeiro
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Visconte
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Tabarroki
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Adriana S S
authors.initials: AS
authors.lastname: Duarte
authors.affiliation: Laboratory of Investigative and Molecular Pathology, CIPED, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Flávia F C
authors.initials: FF
authors.lastname: Barra
authors.affiliation: Laboratory of Investigative and Molecular Pathology, CIPED, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Vassalo
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Heesun J
authors.initials: HJ
authors.lastname: Rogers
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Ramon V
authors.initials: RV
authors.lastname: Tiu
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: Sara T
authors.initials: ST
authors.lastname: Olalla Saad
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro - Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil; Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil. Electronic address: ftraina@fmrp.usp.br.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D000069439:Dasatinib; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D000068877:Imatinib Mesylate; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D019311:Staurosporine; C059539:midostaurin; D000069439:Dasatinib
keywords: Dasatinib; Familial mastocytosis; Imatinib; K509I KIT mutation; PKC412; Tyrosine kinase inhibitors