title: Myeloid malignancies: mutations, models and management.
abstract: Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX), tumor suppressors (e.g. TP53), and components of the spliceosome (e.g. SF3B1, SRSF2). Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach.
authors: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire; UMR1068 Inserm, Institut Paoli-Calmettes, 27 Bd, Leï Roure, BP 30059, Marseille, 13273, France.
authors: Anne
authors: A
authors: Murati
authors: Mandy
authors: M
authors: Brecqueville
authors: Raynier
authors: R
authors: Devillier
authors: Marie-Joelle
authors: MJ
authors: Mozziconacci
authors: Véronique
authors: V
authors: Gelsi-Boyer
authors: Daniel
authors: D
authors: Birnbaum
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008954:Models, Biological; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism / Q000628:therapy