{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:53:14Z","timestamp":1791175994542,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T00:00:00Z","timestamp":1324425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high\u2010resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (<jats:italic>N<\/jats:italic> = 46) or MDS (<jats:italic>N<\/jats:italic> = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1\u2010Mb region and contained only the <jats:italic>JARID2<\/jats:italic> gene\u2014member of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (<jats:italic>P<\/jats:italic> = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as <jats:italic>EZH2<\/jats:italic>, <jats:italic>AEBP2<\/jats:italic>, and <jats:italic>SUZ12<\/jats:italic>; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of <jats:italic>JARID2<\/jats:italic> and <jats:italic>AEBP2<\/jats:italic>. We observed frequent codeletion of <jats:italic>AEBP2<\/jats:italic> and <jats:italic>ETV6<\/jats:italic>, and similarly, <jats:italic>SUZ12<\/jats:italic> and <jats:italic>NF1<\/jats:italic>. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member <jats:italic>SUZ12<\/jats:italic>. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. Am. J. Hematol. 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.22257","type":"journal-article","created":{"date-parts":[[2011,11,18]],"date-time":"2011-11-18T13:05:58Z","timestamp":1321621558000},"page":"245-250","source":"Crossref","is-referenced-by-count":97,"title":["Frequent deletions of <i>JARID2<\/i> in leukemic transformation of chronic myeloid malignancies"],"prefix":"10.1002","volume":"87","author":[{"given":"Ana","family":"Puda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena D.","family":"Milosevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Klampfl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashot 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