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.
Key words: Myeloproliferative neoplasm, SOCS1, SOCS3, Secondary erythrocytosis/thrombocythemia
Amac: Esansiyel trombositemi (ET), polisitemia vera (PV), primer miyelofibrozis (PMF) gibi miyeloproliferatif neoplazmlar (MPN) kazanilmis klonal hematopoetik kok hucre hastaligi olup multipotent hematopoietik kok hucreden koken ahrlar. SOCS1 ve SOCS3 genleri JAK/STAT sinyal yolaginin negatif duzenleyicileridir. Bu calismada MPN ve sekonder eritrositoz/trombositemi patogenezinde bu genlerin promotor metilasyonunu incelemeyi amacladik.
Gerec ve Yontemler: SOCS1, SOCS3 genlerinin promotor metilasyonu, metilasyon spesififk PCR ile incelendi. PCR urunleri agaroz jel elektroforezinde analiz edildi.
Bulgular: SOCS1 geninde CpG adaciklarinda hastalikla i1iski1i metilasyon bulunamadi. 19 PV olgusunun 5'inde (%26,3), 21 ET olgusunun 2'sinde (%9,5), 5 PMF olgusunun (%20), 42 sekonder eritrositoz/trombositemi olgusunun 9'unda (%21,4) SOCS3 promotor metilasyonu saptandi.
Sontic: SOCS3 geni promotor metilasyonu MPN ve sekonder eritrositoz/trombositemi patogenezinde etkili olarak gorunmektedir.
Anahtar Sozcukler: Miyeloproliferatif Neoplazi, SOCS1; SOCS3; Sekonder eritrositoz/trombositemi
Myeloproliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), although the MPNs on the whole have a much better prognosis than these conditions. The classic MPNs are polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and chronic myelogenous leukemia (CML). They were originally grouped together based on their shared phenotype of myeloproliferation (1). All of these neoplasms are acquired clonal hematopoietic stem cell disorders, originating from a multipotent hematopoietic stem cell. Cytogenetic and/or molecular genetic analyses are mandatory for differential diagnosis. Apart from the BCR/ABL rearrangement in CML, the JAK2 and MPL mutations play a crucial role in the pathogenesis of PV, ET, and PMF (2), (3).
The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell (4). The suppressor of cytokine signaling (SOCS) proteins inhibit the cytokine signaling cascade by using the JAK/STAT pathway in a cell (5). Expression of SOCS1 and SOCS3 genes leads to reduced JAK and STAT phosphorylation via binding...