Abstract
SETBP1 is a SET-binding protein regulating self-renewal potential through HOXA-protein activation. Somatic SETBP1 mutations were identified by whole exome sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute myeloid leukemia (sAML). Surprisingly, its recurrent somatic activated mutations are located at the identical positions of germline mutations reported in congenital Schinzel-Giedion syndrome. In general, somatic SETBP1 mutations have a significant clinical impact on the outcome as poor prognostic factor, due to downstream HOXA-pathway as well as associated aggressive types of chromosomal defects (-7/del(7q) and i(17q)), which is consistent with wild-type SETBP1 activation in aggressive types of acute myeloid leukemia and leukemic evolution. Biologically, mutant SETBP1 attenuates RUNX1 and activates MYB. The studies of mouse models confirmed biological significance of SETBP1 mutations in myeloid leukemogenesis, particularly associated with ASXL1 mutations. SETBP1 is a major oncogene in myeloid neoplasms, which cooperates with various genetic events and causes distinct phenotypes of MDS/MPN and sAML.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.