title: [Not Available].
abstract: BIOLOGICAL ASPECTS OF JAK/STAT SIGNALING IN BCR-ABL-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS: Myeloproliferative disorders more recently named Myeloproliferative neoplasms (MPN) display several clinical entities: chronic myeloid leukemia (CML), the classical MPN including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and atypical and unclassifiable NMP. The term MPN is mostly used for classical BCR-ABL-negative (myeloproliferative disorder) (ET, PV, PMF). These are clonal diseases resulting from the transformation of an hematopoietic stem cell and leading to an abnormal production of myeloid cells. The genetic defects responsible for the myeloproliferative abnormalities are called « driver » mutations and all result in deregulation of the cytokine receptor / JAK2 / STAT axis. Among them, JAK2, the thrombopoietin receptor (MPL) and calreticulin (CALR) mutations are found in around 90% of the cases. These driver MPN mutations can be associated with other driver mutations also found in other hematological malignancies, especially in PMFs. These are chronic diseases with major risks being thrombosis, hemorrhage and cytopenias for PMF and the long-term progression to myelofibrosis and the transformation to leukemia. Most recent therapeutic have focused on targeting the JAK2 signaling pathway directly by inhibitors of JAK2 or indirectly. Interferon a allows in some cases hematologic and molecular remission patients.
authors: Inserm UMR 1170, Gustave Roussy, Villejuif, 94805, France; Université Paris-Saclay, UMR 1170, Gustave Roussy, Villejuif, 94805, France; Gustave Roussy, UMR 1170, Villejuif, 94805, France.
authors: Matthieu
authors: M
authors: Mosca
authors: Signal Transduction & Molecular Hematology Unit, Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; De Duve Institute, Université catholique de Louvain, Brussels B-1200, Belgium.
authors: Gaëlle
authors: G
authors: Vertenoeil
authors: Inserm UMR 1170, Gustave Roussy, Villejuif, 94805, France; Université Paris-Saclay, UMR 1170, Gustave Roussy, Villejuif, 94805, France; Gustave Roussy, UMR 1170, Villejuif, 94805, France.
authors: Katte Rao
authors: KR
authors: Toppaldoddi
authors: Inserm UMR 1170, Gustave Roussy, Villejuif, 94805, France; Université Paris-Saclay, UMR 1170, Gustave Roussy, Villejuif, 94805, France; Gustave Roussy, UMR 1170, Villejuif, 94805, France.
authors: Isabelle
authors: I
authors: Plo
authors: Inserm UMR 1170, Gustave Roussy, Villejuif, 94805, France; Université Paris-Saclay, UMR 1170, Gustave Roussy, Villejuif, 94805, France; Gustave Roussy, UMR 1170, Villejuif, 94805, France. Electronic address: william.vainchenker@gustaveroussy.fr.
authors: William
authors: W
authors: Vainchenker
mesh_terms: D037282:Calreticulin / Q000235:genetics; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics; D050791:STAT Transcription Factors / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D037282:Calreticulin; D016898:Interferon-alpha; D053628:Receptors, Thrombopoietin; D050791:STAT Transcription Factors; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Calreticulin; Calréticuline; Epigenetic mutations; JAK2V617F; MPL; Mutations; Myeloproliferative; Néoplasmes; d'épigénétique; myéloprolifératifs; neoplasms