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With a median follow\u2010up of 7\u00b72\u00a0years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, <jats:italic>CALR<\/jats:italic> genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0\u00b713, 95% confidence interval (CI): 0\u00b72\u20130\u00b79, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7039], whereas <jats:italic>JAK2<\/jats:italic> V617F showed borderline significance for higher risk (SHR: 2\u00b705, 95% CI: 0\u00b79\u20134\u00b76, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b709). Myelofibrotic transformation increased leukaemic risk, except in <jats:italic>CALR<\/jats:italic>\u2010mutated patients. Next generation sequencing of 51 genes at the time of transformation showed additional mutations (median number: 3; range: 1\u20135) in 25 out of 29 (86%) assessable cases. Mutations (median: 1; range: 1\u20133) were detected in 67% of paired samples from the chronic phase. Leukaemia appeared in a <jats:italic>JAK2<\/jats:italic> V617F negative clone in 17 (58%) cases, eleven of them being previously <jats:italic>JAK2<\/jats:italic> V617F\u2010positive. <jats:italic>JAK2<\/jats:italic> V617F\u2010mutated leukaemia was significantly associated with complex karyotype and acquisition of <jats:italic>TP53<\/jats:italic> mutations, whereas <jats:italic>EZH2<\/jats:italic> and <jats:italic>RUNX1<\/jats:italic> mutations were more frequent in <jats:italic>JAK2<\/jats:italic> V617F\u2010negative leukaemia. Survival was longer in <jats:italic>JAK2<\/jats:italic> V617F\u2010unmutated leukaemia (343\u00a0days vs. 95\u00a0days, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7003). In conclusion, <jats:italic>CALR<\/jats:italic> genotype is associated with a lower risk of leukaemic transformation. Leukaemia arising in a <jats:italic>JAK2<\/jats:italic> V617F\u2010negative clone is <jats:italic>TP53<\/jats:italic> independent and shows better survival.<\/jats:p>","DOI":"10.1111\/bjh.14762","type":"journal-article","created":{"date-parts":[[2017,5,24]],"date-time":"2017-05-24T00:32:09Z","timestamp":1495585929000},"page":"764-771","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6387-4619","authenticated-orcid":false,"given":"Alberto","family":"Alvarez\u2010Larr\u00e1n","sequence":"first","affiliation":[{"name":"Haematology Department Hospital del Mar\u2010IMIM Universidad Aut\u00f3noma de Barcelona Barcelona 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