Mutations in SETBP 1 are recurrent in myelodysplastic syndromes and often coexist with cytogenetic markers associated with disease progression

Summary Whole exome sequencing was performed in a patient with myelodysplastic syndrome before and after progression to acute myeloid leukaemia. Mutations in several genes, including SETBP 1 , were identified following leukaemic transformation. Screening of 328 patients with myeloid disorders revealed SETBP 1 mutations in 14 patients (4·3%), 7 of whom had −7/del(7q) and 3 had i(17)(q10), cytogenetic markers associated with shortened overall survival and increased risk of leukaemic evolution. SETBP 1 mutations were frequently acquired at the time of leukaemic evolution, coinciding with increase of leukaemic blasts. These data suggest that SETBP 1 mutations may play a role in MDS and chronic myelomonocytic leukaemia disease progression.