| Written | 2012-09 | Ion Cristóbal, Laura García-Orti, María D Odero |
| | Translational Oncology Division, Health Research Institute, Oncology Department, University Hospital Fundacion Jimenez Diaz, Autonomous University of Madrid, E-28040 Madrid, Spain (IC); Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, E-31008 Pamplona, Spain (LGO, MDO); Department of Genetics, School of Sciences, University of Navarra E-31008 Pamplona, Spain (MDO) |
| Description | Two isoforms: variant a (1596 amino acids); variant b (242 amino acids). |
| Expression | Expressed in numerous tissues. |
| Localisation | Predominantly in the nucleus (Minakuchi et al., 2001; Cristóbal et al., 2010). |
| Function | SETBP1 overexpression promotes leukemogenesis by enhancing full-length SET protein and then impairing the phosphatase activity of the tumor suppressor PP2A in acute myeloid leukaemia. In addition, defects in SETBP1 have been described as the cause of Schinzel-Giedion syndrome. |
| Homology | The protein contains a region homologous to the dimerization domain of the SKI oncoprotein, six PEST sequences, three AT-hook DNA binding domains, a SET-binding domain and three nuclear localization signals. |
| Note | |
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| Entity | Pediatric T-cell acute lymphoblastic leukemia (T-ALL) (Panagopoulos et al., 2007) |
| Cytogenetics | t(11;18)(p15;q12); only one case decribed so far. |
| Hybrid/Mutated Gene | 5' NUP98 - 3' SETBP1 |
| Abnormal Protein | The NUP98-SETBP1 fusion protein consists in the exon 12 of NUP98 fused in-frame with exon 5 of SETBP1. |
| Oncogenesis | SETBP1/NUP98 expression was not detected, suggesting that the NUP98/SETBP1 transcript is pathogenetically important. |
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| Entity | Schinzel-Giedion syndrome |
| Prognosis | Defects in SETBP1 caused by the presence of the novo mutations have been described as the cause of Schinzel-Giedion midface retraction syndrome. |
| Cytogenetics | Normal karyotype. |
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| Entity | Acute myeloid leukemia (AML) |
| Prognosis | SETBP1 overexpression associates with worse overall survival specially in the subgroup of elderly patients (older than 60 years). |
| Cytogenetics | The presence of a t(12;18)(p13;q12) has been describe in one case with AML secondary to myelodysplastic syndrome (figure 1) (Cristóbal et al., 2010), and in one case with AML secondary to primary myelofibrosis (Albano et al., 2012). |
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| Figure 1. |
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| Oncogenesis | SETBP1 overexpression promotes leukemogenesis by enhancing full-length SET protein and then impairing the phosphatase activity of the tumor suppressor PP2A through the formation of a SETBP1-SET-PP2A complex. |
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| SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia. |
| Albano F, Anelli L, Zagaria A, Coccaro N, Casieri P, Minervini A, Specchia G. |
| J Hematol Oncol. 2012 Aug 8;5:48. doi: 10.1186/1756-8722-5-48. |
| PMID 22873195 |
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| SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia. |
| Cristobal I, Blanco FJ, Garcia-Orti L, Marcotegui N, Vicente C, Rifon J, Novo FJ, Bandres E, Calasanz MJ, Bernabeu C, Odero MD. |
| Blood. 2010 Jan 21;115(3):615-25. Epub 2009 Nov 16. |
| PMID 19965692 |
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| De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. |
| Hoischen A, van Bon BW, Gilissen C, Arts P, van Lier B, Steehouwer M, de Vries P, de Reuver R, Wieskamp N, Mortier G, Devriendt K, Amorim MZ, Revencu N, Kidd A, Barbosa M, Turner A, Smith J, Oley C, Henderson A, Hayes IM, Thompson EM, Brunner HG, de Vries BB, Veltman JA. |
| Nat Genet. 2010 Jun;42(6):483-5. Epub 2010 May 2. |
| PMID 20436468 |
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| Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET. |
| Minakuchi M, Kakazu N, Gorrin-Rivas MJ, Abe T, Copeland TD, Ueda K, Adachi Y. |
| Eur J Biochem. 2001 Mar;268(5):1340-51. |
| PMID 11231286 |
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| Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12). |
| Panagopoulos I, Kerndrup G, Carlsen N, Strombeck B, Isaksson M, Johansson B. |
| Br J Haematol. 2007 Jan;136(2):294-6. |
| PMID 17233820 |
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| SETBP1 mutations in two Thai patients with Schinzel-Giedion syndrome. |
| Suphapeetiporn K, Srichomthong C, Shotelersuk V. |
| Clin Genet. 2011 Apr;79(4):391-3. doi: 10.1111/j.1399-0004.2010.01552.x. |
| PMID 21371013 |
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