{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:35:53Z","timestamp":1787841353770,"version":"build-2784847793"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012021","name":"Iran University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003968","name":"Iran National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives\/background:<\/jats:title>\n                    <jats:p>\n                      Myelodysplastic syndromes (MDSs) are a heterogeneous disease in terms of clinical course and response to therapy. Epigenetic changes are the primary mechanism of MDS pathogenesis.\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      genes play significant roles in normal cellular mechanisms and are also known as tumor suppressor genes. We aimed to clarify the correlation of epigenetic changes in these genes with clinicopathologic findings in MDS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A total of 54 newly diagnosed MDS patients referred to Shariati and Firouzgar Hospitals (Tehran, Iran) were included in the study from 2013 to 2015, comprising the following cases: 26 with refractory cytopenia with unilineage dysplasia, 10 with refractory cytopenia with multilineage dysplasia, four refractory anemia with excess blasts-1 (RAEB-1), 11 refractory anemia with excess blasts-2 (RAEB-2), and three MDS associated with isolated deletion (5q-). Risk groups were determined according to the Revised International Prognostic Scoring System (IPSS-R). The methylation status of\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      promoters were determined by methylation-sensitive high-resolution melting analysis of sodium bisulfite-converted DNA. Expressions of\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      , and GAPDH were measured by quantitative real-time polymerase chain reaction and fold changes were calculated using the \u0394\u0394CT method.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Statistical analysis revealed no promoter methylation of\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      in healthy control specimens.\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      promoter methylation was associated with high-risk World Health Organization subgroups (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = .017), high-risk IPSS-R (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = .007), high-risk cytogenetics (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = .045), and more than 5% blasts in bone marrow (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = .001).\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      promoter methylation was correlated with more than 5% blasts in bone marrow (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = .009).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Promoter methylation of\n                      <jats:italic toggle=\"yes\">CHEK2<\/jats:italic>\n                      and especially\n                      <jats:italic toggle=\"yes\">FOXO3<\/jats:italic>\n                      is associated with adverse clinicopathological findings and disease progression in MDS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.hemonc.2019.11.004","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T12:43:11Z","timestamp":1584535391000},"page":"214-219","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Epigenetic changes in FOXO3 and CHEK2 genes and their correlation with clinicopathological findings in myelodysplastic syndromes"],"prefix":"10.4103","volume":"13","author":[{"given":"Mohammad 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