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Recently, a RET (exon 12) rearrangement with FGFR1OP [fibroblast growth factor receptor 1 (FGFR1) oncogene partner] (exon 12) was identified in one chronic myelomonocytic leukemia (CMML) patient. We report the molecular cloning and functional characterization of a novel FGFR1OP (exon 11)\u2010RET (exon 11) gene fusion event (named FGFR1OP\u2010RET), mediated by a reciprocal translocation t(6; 10)(q27; q11), in a patient affected by primary myelofibrosis (PMF) with secondary acute myeloid leukemia (AML). The FGFR1OP\u2010RET fusion protein displayed constitutive tyrosine kinase and transforming activity in NIH3T3 fibroblasts, and induced IL3\u2010independent growth and activation of PI3K\/STAT signaling in hematopoietic Ba\/F3 cells. FGFR1OP\u2010RET supported cytokine\u2010independent growth, protection from stress and enhanced self\u2010renewal of primary murine hematopoietic progenitor and stem cells in\u00a0vitro. In\u00a0vivo, FGFR1OP\u2010RET caused a spectrum of disease phenotypes, with &gt;50% of mice showing a fatal myeloproliferative disorder (MPD). Other phenotypes were leukemia transplantable in secondary recipients, dramatic expansion of the mast cell lineage, and reduction of repopulating activity upon lethal irradiation. In conclusion, FGFR1OP\u2010RET chimeric oncogenes are endowed with leukemogenic potential and associated to myeloid neoplasms (CMML and PMF\/AML).<\/jats:p>","DOI":"10.1016\/j.molonc.2013.11.004","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T03:23:48Z","timestamp":1385004228000},"page":"221-231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Functional characterization of a novel FGFR1OP\u2010RET rearrangement in hematopoietic malignancies"],"prefix":"10.1002","volume":"8","author":[{"given":"Daniela","family":"Bossi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Carlomagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Pallavicini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Pruneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Trubia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Rafaniello","family":"Raviele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Anaganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Christina","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Viale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Di Fiore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Minucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210757"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.109"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0596-606"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(00)00136-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040910303"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-052410-090317"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08381.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2008.001214"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600109"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03546"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-311019"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2644"},{"key":"e_1_2_9_14_1","first-page":"159","article-title":"Myeloproliferative neoplasia: a review of clinical criteria and treatment","volume":"70","author":"Koopmans S.M.","year":"2012","journal-title":"Neth. 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