title: Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2.
abstract: We identified 13 new gene expression markers that were elevated and one marker, ANKRD15, that was down-regulated in patients with polycythemia vera (PV). These 14 markers, as well as the previously described PRV1 and NF-E2, exhibited the same gene expression alterations also in patients with exogenously activated granulocytes due to sepsis or granulocyte colony-stimulating factor (G-CSF) treatment. The recently described V617F mutation in the Janus kinase 2 (JAK2) gene allows defining subclasses of patients with myeloproliferative disorders based on the JAK2 genotype. Patients with PV who were homozygous or heterozygous for JAK2-V617F exhibited higher levels of expression of the 13 new markers, PRV1, and NF-E2 than patients without JAK2-V617F, whereas ANKRD15 was down-regulated in these patients. Our results suggest that the alterations in expression of the markers studied are due to the activation of the Jak/signal transducer and activator of transcription (STAT) pathway through exogenous stimuli (sepsis or G-CSF treatment), or endogenously through the JAK2-V617F mutation.
authors.affiliation: Experimental Hematology, Department of Research, Division of Clinical Hematology, Division of Pneumology, Basel University Hospital, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Soon-Siong
authors.initials: SS
authors.lastname: Teo
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Buser
authors.forename: Martin
authors.initials: M
authors.lastname: Brutsche
authors.forename: Ralph
authors.initials: R
authors.lastname: Tiedt
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D017354:Point Mutation; D011087:Polycythemia Vera / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D003598:Cytoskeletal Proteins; C467739:KANK1 protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2