Molecular basis of mast cell disease.
Mastocytosis is an incurable and sometimes fatal haematological disorder grossly described as the accumulation of abnormal mast cells in the bone marrow and other organs causing tissue and organ damage. The clinical manifestations of this disease are extremely variable; disease phenotypes range from indolent to aggressive, and often present with associated non-mast cell haematological disorders (AHNMD), mainly myeloproliferative neoplasm and myelodysplastic syndromes. Recent efforts to genetically dissect the mechanisms that define aggressive and non-aggressive mastocytosis have generated a list of recurrent somatic mutations in mastocytosis patients that are associated with and may predict the evolution towards aggressive disease phenotypes. Here we review these mutations and discuss the molecular mechanisms associated with these mutations in an effort to better understand the biology of this disease and to predict its onset and evolution, with the ultimate goal of devising new and improved treatment strategies.
Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Centre de Référence des Mastocytoses, Institut Paoli-Calmettes, Aix-Marseille Université UM 105, CNRS, UMR7258, Marseille, France. Electronic address: erinn.soucie@inserm.fr.
Erinn
E
Soucie
Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Centre de Référence des Mastocytoses, Institut Paoli-Calmettes, Aix-Marseille Université UM 105, CNRS, UMR7258, Marseille, France.
Fabienne
F
Brenet
Inserm U1068, Centre de Recherche en Cancérologie de Marseille, Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Centre de Référence des Mastocytoses, Institut Paoli-Calmettes, Aix-Marseille Université UM 105, CNRS, UMR7258, Marseille, France. Electronic address: patrice.dubreuil@inserm.fr.
Patrice
P
Dubreuil
D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008407:Mast Cells / Q000276:immunology*; D008415:Mastocytosis / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D000072260:RNA Splicing Factors; D012097:Repressor Proteins / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF
C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D000072260:RNA Splicing Factors; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C541081:TET2 protein, human; D019009:Proto-Oncogene Proteins c-kit
Epigenetic; Mast cells; Mastocytosis; Mutations; Splicing