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SETBP1 mutation analysis in 944 patients with MDS and AML

Leukemia volume 27, pages 2072–2075 (2013)Cite this article

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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

To evaluate SETBP1 mutations in de novo AML and MDS, we analyzed a total of 944 patients with MDS and AML. This group consisted of 425 de novo AML patients (excluding AML M3) who entered the multicenter treatment trials AML SHG 01996 (ClinicalTrials Identifier NCT00209833, June 1999 to September 2004) or AML SHG 02957, 8 (February 1995 to May 1999), 326 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for sAML (n=170) or primary MDS (n=156), and 193 primary MDS patients not undergoing intensive therapy or allogeneic HSCT as previously reported.9 Most samples were from bone marrow. The majority of transplant patients had an unrelated donor (n=246) compared with 80 patients with a related donor. Standard conditioning was performed in 51 patients, while 275 received reduced intensity conditioning. Informed consent was obtained from all patients in accordance with the Declaration of Helsinki. This study was approved by the Institutional Review Board of Hannover Medical School.

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Acknowledgements

This study was supported by the Deutsche Krebshilfe e.V (grant No. 109003), grant No. DJCLS R 10/22 from the Deutsche-José-Carreras Leukämie-Stiftung e.V; grant No. M 47.1 from the H W and J Hector Stiftung, the Dieter-Schlag-Stiftung grant from 2011, the German Federal Ministry of Education and Research grant 01EO0802, DFG grants HE 5240/4-1, HE 5240/5-1 and TH 1779/1-1, HiLF grant from Hannover Medical School and grant from the MHH Tumorstiftung.

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Authors and Affiliations

  1. Department of Hematology, Hemostasis, Oncology and HSCT, Hannover Medical School, Hannover, Germany

    F Thol, K J Suchanek, C Koenecke, M Stadler, S Kade, P Löffeld, S Banihosseini, J Krauter, A Ganser & M Heuser

  2. Medizinische Klinik und Poliklinik I, Universtitätsklinikum Carl Gustav Carus, Dresden, Germany

    U Platzbecker & C Thiede

  3. Klinik für Hämatologie, Onkologie und Klinische Immunologie, Heinreich Heine University, Düsseldorf, Germany

    T Schroeder & G Kobbe

  4. Department of Internal Medicine III, University of Frankfurt, Frankfurt, Germany

    G Bug & O Ottmann

  5. Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany

    W-K Hofmann

  6. Department of HSCT, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    N Kröger

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  1. F Thol
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  2. K J Suchanek
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  8. G Kobbe
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  9. S Kade
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  14. W-K Hofmann
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  15. J Krauter
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  17. A Ganser
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  18. M Heuser
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Correspondence to F Thol.

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Thol, F., Suchanek, K., Koenecke, C. et al. SETBP1 mutation analysis in 944 patients with MDS and AML. Leukemia 27, 2072–2075 (2013). https://doi.org/10.1038/leu.2013.145

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