Role of SOCS3 Promoter Methylation in The Pathogenesis of Myeloproliferative Neoplasms and Secondary/Reactive Erythrocytosis/Thrombocythemia. D. TORUN1, O. NEVRUZ2, M. AKYOL3, S. KOZAN1, M. BAHCE1, S. GURAN4, C. BEYAN2 1) Dept. of Medical Genetics, Gulhane Military Medical Faculty, Ankara, Turkey; 2) Dept. of Haematology, Gulhane Military Medical Faculty, Ankara, Turkey; 3) Dept. of Biostatistics, Gulhane Military Medical Faculty, Ankara, Turkey; 4) Dept. of Medical Biology, Gulhane Military Medical Faculty, Ankara, Turkey.
Myeloproliferative neoplasms (MPN) like essential thrombocythemia (ET), polyctyhemia vera (PV) and primary myelofibrosis (PMF) are acquired clonal hematopoietic stem cell disorders and originate from a multipotent hematopoietic stem cell. MPNs demonstrate phenotypic/genotypic similarity with each other. The diagnosis of MPNs is made by step by step elimination of the other clinical disorders. The lack of specific molecular marker makes difficult the differential diagnosis. Hitherto, a few genetic aberrations have been shown which are related with MPNs. Single nucleotide polymorphisms at various loci and somatic mutations, such as those in JAK2 V617F, MPL W515L/K, exon12 JAK2 may contribute to the pathogenesis of MPNs. JAK2 V617F mutation is responsible for most of the PV, ET and PMF patients. Despite the high prevalence of JAK2 V617F mutation, several question still remains. For example, how do some patients develop MPNs in tha absence of JAK2 V617F mutation? SOCS1 and SOCS3 genes are negative regulators of JAK/STAT signal pathway. Promoter methylation of these genes may deteriorate the inhibitor effect and may cause the development of MPNs. For this purpose, it was aimed to investigate the promoter methylation of SOCS1 and SOCS3 genes with methylation specific polymerase chain reaction (MS-PCR). No disease-specific CpG island methylation of SOCS1 was observed. Hypermethylation of the SOCS3 promoter was identified in 5 of 19 (26,3%) PV, 2 of 21 (9,5%) ET, 1 of 5 (20%) PMF and 9 of 42 (21,4%) secondary/reactive erythrocytosis/thrombositosis. As a result of this study, promoter methylation of SOCS3 gene suggesting a possible role for SOCS3 methylation in the pathogenesis of MPNs and secondary/reactive erythrocytosis/thrombositosis.
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