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 Blood, 15 November 2005, Vol. 106, No. 10, pp. 3374-3376.
Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-05-1889.

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CLINICAL TRIALS AND OBSERVATIONS
Brief report

Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2

Robert Kralovics, Soon-Siong Teo, Andreas S. Buser, Martin Brutsche, Ralph Tiedt, Andre Tichelli, Francesco Passamonti, Daniela Pietra, Mario Cazzola, and Radek C. Skoda

From the Experimental Hematology, Department of Research, Division of Clinical Hematology, Division of Pneumology, and Division of Diagnostic Hematology, Basel University Hospital, Basel, Switzerland; and Division of Hematology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy.

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.


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Related Article in Blood Online:

V617F "JAKs" up myeloproliferative signal
Ayalew Tefferi
Blood 2005 106: 3335-3336. [Full Text] [PDF]





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