LAUSR

OBJECTIVE Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation is initiated by mutations in the JAK2 gene. This activation is in turn, a vital pathogenetic mechanism in myeloproliferative neoplasms (MPNs). However, several factors affect the pathogenesis of MPNs other than the JAK2 gene mutations, such as the downregulation of cytokine signaling (SOCS) proteins, which are potent inhibitors of the JAK/STAT pathway. Therefore, we hypothesized that the regulation of SOCS protein system might be a possible pathogenetic mechanism of MPNs through activating the JAK/STAT pathway. PATIENTS AND METHODS Our study aimed to investigate the status of the Suppressors of cytokine signaling 1 (SOCS1) in 125 MPNs specimens at the level of mutated points. The acquired mutations, aberrant expression, and/or CpG island hypermethylation of SOCS1 were analyzed among Philadelphia-negative myeloproliferative neoplasm patients. RESULTS SOCS1 was identified in 20.0% of all patients with Philadelphia-negative myeloproliferative neoplasm. At the diagnosis, the prevalence of methylation was 41.0% for Polycythaemia Vera (PV), 27.7% for Essential Thrombocythaemia (ET), and 6.6% for Primary Myelofibrosis (PMF). The methylation was not detected in 20 healthy adult people. A significant association was found between disease groups (p=.077). The presence of methylated SOCS1 was found to be significantly correlated with age (p=.005), total RBCs count (p=.019), hemoglobin (Hb) concentration (p=.002), and Hematopoietic cell transplant (HCT) (p=.007) in PV patients. However, the presence of methylated SOCS1 was found to be significantly associated with age (p=.012), total RBCs count (p=.022), Hb concentration (p=.024), HCT (p=.033), and platelets count (p=.037) in ET patients. Moreover, the presence of methylated SOCS1 was significantly associated with Hb concentration (p=.046) and HCT (p=.040) in PMF patients. CONCLUSIONS We concluded that the activation of the JAK/STAT signaling pathway in alternative or with JAK2 mutations leads to SOCS1 hypermethylation, which could represent a potential therapeutic target.