Turk J Hematol. 2013; 30(1): 13-18 | DOI: 10.4274/tjh.98474

Methylation of SOCS3 in Myeloproliferative Neoplasms and Secondary Erythrocytosis/Thrombocythemia

Deniz Torun¹, Oral Nevruz², Mesut Akyol³, Salih Kozan¹, Muhterem Bahçe¹, Şefik Güran⁴, Cengiz Beyan^2
1Gülhane Military Medical Faculty, Department Of Medical Genetics, Ankara, Turkey
²Gülhane Military Medical Faculty, Department Of Hematology, Ankara, Turkey
³Gülhane Military Medical Faculty, Department Of Biostatistics, Ankara, Turkey
⁴Gülhane Military Medical Faculty, Department Of Medical Biology, Ankara, Turkey

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.
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.

Keywords: Myeloproliferative neoplasm, SOCS1, SOCS3, Secondary erythrocytosis/thrombocythemia

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Miyeloproliferatif Neoplazmlar ve Sekonder Eritrositoz/Trombositemide SOCS3 Metilasyonu

Deniz Torun¹, Oral Nevruz², Mesut Akyol³, Salih Kozan¹, Muhterem Bahçe¹, Şefik Güran⁴, Cengiz Beyan^2
1Gülhane Askeri Tıp Fakultesi, Tıbbi Genetik Bilim Dalı, Ankara
²Gülhane Askeri Tıp Fakultesi, Hematoloji Bilim Dalı, Ankara
³Gülhane Askeri Tıp Fakultesi, Biyoistatistik Bilim Dalı, Ankara
⁴Gülhane Askeri Tıp Fakultesi, Tıbbi Biyoloji Ana Bilim Dalı, Ankara

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.
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.

Anahtar Kelimeler: Miyeloproliferatif Neoplazi, SOCS1, SOCS3; Sekonder eritrositoz/trombositemi

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