SETBP1 mutation analysis in 944 patients with MDS and AML

Abstract

Germline mutations in SET binding protein 1 (SETBP1) have been reported in children with Schinzel–Giedion syndrome, a congenital condition characterized by facial as well as skull abnormalities, hydronephrosis and developmental delay.1 Recently, exome sequencing identified recurrent somatic mutations in SETBP1 in atypical chronic myeloid leukemia (aCML).2 Of 70 examined patients with aCML, 17 patients (24%) were found to carry mutations in SETBP1. These mutations clustered between codon 858 and 871, all located in the SKI-homologous region of SETBP1. This is a highly conserved region with unknown biological function. In aCML, SETBP1 mutations were associated with worse prognosis and a higher white blood cell count compared with patients with wild-type SETBP1.2 A search for the presence of SETBP1 mutations in other hematological malignancies closely related to aCML, revealed the presence of SETBP1 mutations in chronic neutrophilic leukemia, chronic myelomonocytic leukemia, unclassified myelodysplastic syndromes/myeloproliferative neoplasms and secondary AML (sAML) evolving from MDS at variable frequencies (4–25%).2, 3, 4, 5