SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML

SETBP1 encodes SET-binding protein 1, a binding partner for the multi-function SET protein. This protein is encoded by the SET nuclear oncogene and is involved in apoptosis, transcription and nucleosome assembly. 1 The proposed functional outcome of this interaction is based on in vitro studies that demonstrate a protection of SET protein from protease cleavage that results in inhibition of protein phosphatase 2A activity, leading to higher rates of cell proliferation. 1 Initial identification of germline SETBP1 alterations affecting amino-acid residues between 858 and 871 have been described in patients with Schinzel–Giedion syndrome, associated with a congenital phenotype including mental retardation and facial deformities. 2