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However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We searched for mutations in the <jats:italic>ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2<\/jats:italic> and <jats:italic>WT1<\/jats:italic> genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Mutations in <jats:italic>ASXL1<\/jats:italic> and <jats:italic>CBL<\/jats:italic> were frequent in refractory anemia with excess of blasts. Mutations in <jats:italic>TET2<\/jats:italic> occurred with similar frequency in MDSs and AMLs and associated equally with either <jats:italic>ASXL1<\/jats:italic> or <jats:italic>NPM1<\/jats:italic> mutations. Mutations of <jats:italic>RUNX1<\/jats:italic> were mutually exclusive with <jats:italic>TET2<\/jats:italic> and combined with <jats:italic>ASXL1<\/jats:italic> but not with <jats:italic>NPM1<\/jats:italic>. Mutations in <jats:italic>FLT3 (<\/jats:italic>mutation and internal tandem duplication), <jats:italic>IDH1<\/jats:italic>, <jats:italic>IDH2<\/jats:italic>, <jats:italic>NPM1<\/jats:italic> and <jats:italic>WT1<\/jats:italic> occurred primarily in AMLs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-10-401","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T19:02:12Z","timestamp":1280862132000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias"],"prefix":"10.1186","volume":"10","author":[{"given":"Julien","family":"Rocquain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Carbuccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Trouplin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Raynaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Murati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meyer","family":"Nezri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoulika","family":"Tadrist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylviane","family":"Olschwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Vey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Birnbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Gelsi-Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Joelle","family":"Mozziconacci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,8,2]]},"reference":[{"key":"2200_CR1","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1056\/NEJMra0902908","volume":"361","author":"A Tefferi","year":"2009","unstructured":"Tefferi A, Vardiman JW: Myelodysplastic syndromes. 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