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We report the results of targeted next\u2010generation sequencing on three patients with <jats:italic><jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>1 <\/jats:italic><jats:styled-content style=\"fixed-case\">FPDMM<\/jats:styled-content> who developed acute myeloid leukaemia or myelodysplastic syndromes (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an <jats:italic><jats:styled-content style=\"fixed-case\">SRSF<\/jats:styled-content>2<\/jats:italic> p.P95R variant, prior to his <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> diagnosis, when he developed an additional <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> p.G12D variant. His sister presented to us with <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>, with a <jats:italic><jats:styled-content style=\"fixed-case\">TET<\/jats:styled-content>2<\/jats:italic> p.S471fs and identical <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> p.G12D variant. The third patient, from another family, had an additional <jats:italic><jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>1<\/jats:italic> p.R204X and an <jats:italic><jats:styled-content style=\"fixed-case\">NFE<\/jats:styled-content>2<\/jats:italic> p.Q139fs variant at <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> diagnosis. This constitutes the first report of <jats:italic><jats:styled-content style=\"fixed-case\">NFE<\/jats:styled-content>2<\/jats:italic> variants in <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> without extramedullary disease and <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> variants in <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> in the setting of <jats:styled-content style=\"fixed-case\">FPDMM<\/jats:styled-content>. A systematic review of the literature including our findings distinguishes two genetic landscapes at <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> transformation from <jats:styled-content style=\"fixed-case\">FPDMM<\/jats:styled-content> characterized by either the presence or absence of somatic abnormalities in <jats:italic><jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>1<\/jats:italic> with or without variants in genes usually associated with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in <jats:italic><jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>1<\/jats:italic> needs further confirmation.<\/jats:p>","DOI":"10.1111\/bjh.15990","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T09:12:15Z","timestamp":1558689135000},"page":"724-734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Longitudinal sequencing of <i><scp>RUNX<\/scp>1<\/i> familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies"],"prefix":"10.1111","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6155-3253","authenticated-orcid":false,"given":"Bruno K. L.","family":"Duarte","sequence":"first","affiliation":[{"name":"INCT do Sangue Hemocentro UNICAMP University of Campinas Campinas SP Brazil"},{"name":"Department of Internal Medicine Faculty of Medical Sciences University of Campinas FCM Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela G.","family":"Yamaguti\u2010Hayakawa","sequence":"additional","affiliation":[{"name":"INCT do Sangue Hemocentro UNICAMP University of Campinas Campinas SP Brazil"},{"name":"Department of Internal Medicine Faculty of Medical Sciences University of Campinas FCM Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel S.","family":"Medina","sequence":"additional","affiliation":[{"name":"INCT do Sangue Hemocentro UNICAMP University of Campinas Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00facia H.","family":"Siqueira","sequence":"additional","affiliation":[{"name":"INCT do Sangue Hemocentro UNICAMP University of Campinas Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke","family":"Snetsinger","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando F.","family":"Costa","sequence":"additional","affiliation":[{"name":"INCT do Sangue Hemocentro UNICAMP University of Campinas Campinas SP Brazil"},{"name":"Department of Internal Medicine Faculty of Medical Sciences University of Campinas FCM Campinas SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Rauh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston ON 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