Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2.
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.
Kralovics
Robert
R
Experimental Hematology, Department of Research, Division of Clinical Hematology, Division of Pneumology, Basel University Hospital, Switzerland.
Teo
Soon-Siong
SS
Buser
Andreas S
AS
Brutsche
Martin
M
Tiedt
Ralph
R
Tichelli
Andre
A
Passamonti
Francesco
F
Pietra
Daniela
D
Cazzola
Mario
M
Skoda
Radek C
RC
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
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