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. 2013 Mar;30(1):13-8.
doi: 10.4274/tjh.98474. Epub 2013 Mar 5.

Methylation of SOCS3 in Myeloproliferative Neoplasms and Secondary Erythrocytosis/Thrombocythemia

Deniz Torun  1 , Oral Nevruz  2 , Mesut Akyol  3 , Salih Kozan  1 , Muhterem Bahçe  1 , Sefik Güran  4 , Cengiz Beyan  2
Affiliations

Methylation of SOCS3 in Myeloproliferative Neoplasms and Secondary Erythrocytosis/Thrombocythemia

Deniz Torun et al. Turk J Haematol. 2013 Mar.

Abstract
in English, Turkish

Objective: Myeloproliferative neoplasms (MPNs) like essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are acquired clonal hematopoietic stem cell disorders and originate from a multipotent hematopoietic stem cell. The SOCS1 and SOCS3 genes are negative regulators of the JAK/STAT signal pathway. In this study we investigate the promoter methylation of these genes in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia.

Materials and methods: Promoter methylation of SOCS1 and SOCS3 genes was analyzed with methylation-specific PCR. PCR products were analyzed by agarose gel electrophoresis.

Results: No disease-specific CpG island methylation of SOCS1 was observed. Hypermethylation of the SOCS3 promoter was identified in 5 out of 19 (26.3%) PV cases, 2 out of 21 (9.5%) ET cases, 1 out of 5 (20%) PMF cases, and 9 out of 42 (21.4%) cases of secondary erythrocytosis/thrombocythemia.

Conclusion: The results revealed that promoter methylation of the SOCS3 gene suggests a possible role for SOCS3 methylation in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia.

Conflict of interest: None declared.

Amaç: Esansiyel trombositemi (ET), polisitemia vera (PV), primer miyelofibrozis (PMF) gibi miyeloproliferatif neoplazmlar (MPN) kazanılmış klonal hematopoetik kök hücre hastalığı olup multipotent hematopoietik kök hücreden köken alırlar. SOCS1 ve SOCS3 genleri JAK/STAT sinyal yolağının negatif düzenleyicileridir. Bu çalışmada MPN ve sekonder eritrositoz/trombositemi patogenezinde bu genlerin promotor metilasyonunu incelemeyi amaçladık. Gereç ve Yöntemler: SOCS1, SOCS3 genlerinin promotor metilasyonu, metilasyon spesififk PCR ile incelendi. PCR ürünleri agaroz jel elektroforezinde analiz edildi. Bulgular: SOCS1 geninde CpG adacıklarında hastalıkla ilişkili metilasyon bulunamadı. 19 PV olgusunun 5’inde (%26,3), 21 ET olgusunun 2’sinde (%9,5), 5 PMF olgusunun 1’inde (%20), 42 sekonder eritrositoz/trombositemi olgusunun 9’unda (%21,4) SOCS3 promotor metilasyonu saptandı. Sonuç: SOCS3 geni promotor metilasyonu MPN ve sekonder eritrositoz/trombositemi patogenezinde etkili olarak görünmektedir.

Keywords: Myeloproliferative neoplasm; SOCS1; SOCS3; Secondary erythrocytosis/thrombocythemia.

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Figures

Figure 1
Figure 1. Methylation-specific PCR amplification of SOCS1 promoter region. U: unmethylated, M: methylated, M’: molecular weight marker (100 bp). N1-N2: unmethylated. Presence of bands in control groups indicates the efficacy of bisulfite treatment.
Figure 2
Figure 2. Methylation-specific PCR amplification of SOCS3 promoter region. U: unmethylated, M: methylated, M’: molecular weight marker (100 bp). N1-N2: unmethylated, N3-N4: methylated. Presence of bands in control groups indicates the efficacy of bisulfite treatment.
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References

    1. Wadleigh M, Tefferi A. Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria. Int J Hematol. 2010;91:174–179. - PubMed
    1. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–397. - PubMed
    1. Daly S, Conneally E, Langabeer SE. Identification of MPL W515L/K mutations in patients with primary myelofibrosis and essential thrombocythaemia by allele-specific polymerase chain reaction. Acta Haematol. 2009;121:221–222. - PubMed
    1. Aaronson DS, Horvath CM. A road map for those who don’t know JAK-STAT. Science. 2002;296:1653–1655. - PubMed
    1. Greenhalgh CJ, Hilton DJ. Negative regulation of cytokine signaling. J Leukoc Biol. 2001;70:348–356. - PubMed

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