The clinical impact of DNA methylation frequencies of JAK2 negative regulators in patients with essential thrombocythemia.
Suppressors of cytokine signalling (SOCS) and protein tyrosine phosphatase (PTPN) proteins are negative regulators of Janus Kinase 2 (JAK2). They are thought to be involved in the molecular pathogenesis of essential thrombocythaemia (ET) particularly in patients with unmutated JAK2. In this study we compared DNA methylation of SOCS1, SOCS3 and PTPN6 in peripheral blood cells between 39 ET patients (24 JAK2 V617F mutated) and 22 healthy controls by methylation specific PCR (MSP) and analysed the clinical outcome of patients with respect to DNA methylation. In SOCS1, ET patients showed significantly less methylation (P<0.05) than healthy controls, and in SOCS3 and PTPN6 such a tendency was shown. However, there were no significant differences in the methylation frequencies between JAK2 wildtype and mutated ET patients. In addition, no correlation was detected between methylation of SOCS and PTPN and any clinical outcome parameters. Taken together, regarding the genomic regions investigated our data indicate a minor role of methylation of JAK2 negative regulators for the clinical course of ET.
Department of Internal Medicine I, Elisabethinen Hospital, Linz, Austria. mathilde.foedermayr@elisabethinen.or.at
Mathilde
M
Födermayr
Otto
O
Zach
Maria
M
Huber
Sigrid
S
Machherndl-Spandl
Soraya
S
Wölfl
Hans-Christian
HC
Bösmüller
Sonja
S
Hasenschwandtner
Sonja
S
Burgstaller
Otto
O
Krieger
Dieter
D
Lutz
Ansgar
A
Weltermann
Hanns
H
Hauser
D019175:DNA Methylation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics*
C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6