title: Molecular defects in mastocytosis: KIT and beyond KIT.
abstract: In all variants of mastocytosis, activating KIT mutations are frequently found. In adults, neoplastic mast cells (MCs) cells show the KIT mutation D816V, whereas in children, MCs invading the skin are frequently positive for non-KIT D816V mutations. The clinical course and prognosis of the disease vary among patients with systemic mastocytosis (SM). Additional KIT-independent molecular defects might cause progression. Additional oncogenic lesions have recently been identified in advanced SM. In advanced SM the presence of additional genetic lesions or altered signaling worsening the prognosis might lead to the use of alternative therapies such as combined antisignaling targeted treatments or stem cell transplantation.
authors.affiliation: Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, 61, Avenue du Président Wilson, Cachan 94235, France.
authors.forename: Siham
authors.initials: S
authors.lastname: Bibi
authors.affiliation: Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, 61, Avenue du Président Wilson, Cachan 94235, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Langenfeld
authors.affiliation: Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, 61, Avenue du Président Wilson, Cachan 94235, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jeanningros
authors.affiliation: Signaling, Hematopoiesis and Mechanism of Oncogenesis, Inserm U1068, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France; Institut Paoli-Calmettes, 232, Bd Sainte-Marguerite BP 156, Marseille 13009, France; Aix-Marseille University, UM 105, 27, Bd Leï Roure BP 30059, Marseille 13284, France; CNRS, UMR7258, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brenet
authors.affiliation: Signaling, Hematopoiesis and Mechanism of Oncogenesis, Inserm U1068, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France; Institut Paoli-Calmettes, 232, Bd Sainte-Marguerite BP 156, Marseille 13009, France; Aix-Marseille University, UM 105, 27, Bd Leï Roure BP 30059, Marseille 13284, France; CNRS, UMR7258, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France.
authors.forename: Erinn
authors.initials: E
authors.lastname: Soucie
authors.affiliation: Clinical Hematology Department, Faculty of Medicine and AP-HP Necker-Enfants Malades, Paris Descartes University, 12, Rue de l'École de Médecine, 75006, Paris, France; Faculty of Medicine et AP-HP Necker-Enfants Malades, Mastocytosis Reference Center, 149, Rue de Sèvres, 75015 Paris, Paris Cedex 15 75743, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Faculty of Medicine et AP-HP Necker-Enfants Malades, Mastocytosis Reference Center, 149, Rue de Sèvres, 75015 Paris, Paris Cedex 15 75743, France; Clinical Hematology Department, Hôpital Sud, CHU Amiens, Ave René Laënnec - Salouël, Amiens 80054, France.
authors.forename: Gandhi
authors.initials: G
authors.lastname: Damaj
authors.affiliation: Signaling, Hematopoiesis and Mechanism of Oncogenesis, Inserm U1068, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France; Institut Paoli-Calmettes, 232, Bd Sainte-Marguerite BP 156, Marseille 13009, France; Aix-Marseille University, UM 105, 27, Bd Leï Roure BP 30059, Marseille 13284, France; CNRS, UMR7258, CRCM, 27, Bd Leï Roure BP 30059, Marseille 13009, France; Faculty of Medicine et AP-HP Necker-Enfants Malades, Mastocytosis Reference Center, 149, Rue de Sèvres, 75015 Paris, Paris Cedex 15 75743, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.affiliation: Molecular Oncology and Pharmacology, LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, 61, Avenue du Président Wilson, Cachan 94235, France. Electronic address: arock@ens-cachan.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Arock
mesh_terms: D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008415:Mastocytosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D019089:Stem Cell Factor; D049308:Dioxygenases; C541081:TET2 protein, human; D019009:Proto-Oncogene Proteins c-kit
keywords: ASXL1; KIT; Mutation; Signaling; Spliceosome; Systemic mastocytosis; TET2; Targeted therapy