Abstract
OBJECTIVE: Janus kinase/sig-nal 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 myelop-roliferative neoplasms (MPNs). However, sever-al factors affect the pathogenesis of MPNs oth-er 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 spec-imens at the level of mutated points. The ac-quired mutations, aberrant expression, and/or CpG island hypermethylation of SOCS1 were an-alyzed among Philadelphia-negative myelopro-liferative neoplasm patients.RESULTS: SOCS1 was identified in 20.0% of all patients with Philadelphia-negative myeloprolifer-ative 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 be-tween disease groups (p=.077). The presence of methylated SOCS1 was found to be significant-ly 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 methyl-ated SOCS1 was found to be significantly associ-ated 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 signifi-cantly associated with Hb concentration (p=.046) and HCT (p=.040) in PMF patients.CONCLUSIONS: We concluded that the ac-tivation of the JAK/STAT signaling pathway in alternative or with JAK2 mutations leads to SOCS1 hypermethylation, which could repre-sent a potential therapeutic target.