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Myelodysplasias

SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations

Leukemia volume 27, pages 1852–1860 (2013)Cite this article

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Abstract

Chronic myeloid malignancies are categorized to the three main categories myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs) and MDS/MPN overlap. So far, no specific genetic alteration profiles have been identified in the MDS/MPN overlap category. Recent studies identified mutations in SET-binding protein 1 (SETBP1) as novel marker in myeloid malignancies, especially in atypical chronic myeloid leukemia (aCML) and related diseases. We analyzed SETBP1 in 1 130 patients with MPN and MDS/MPN overlap and found mutation frequencies of 3.8% and 9.4%, respectively. In particular, there was a high frequency of SETBP1 mutation in aCML (19/60; 31.7%) and MDS/MPN unclassifiable (MDS/MPN, U; 20/240; 9.3%). SETBP1 mutated (SETBP1mut) patients showed significantly higher white blood cell counts and lower platelet counts and hemoglobin levels than SETBP1 wild-type patients. Cytomorphologic evaluation revealed a more dysplastic phenotype in SETBP1mut cases as compared with wild-type cases. We confirm a significant association of SETBP1mut with −7 and isochromosome i(17)(q10). Moreover, SETBP1mut were strongly associated with ASXL1 and CBL mutations (P<0.001 for both) and were mutually exclusive of JAK2 and TET2 mutations. In conclusion, SETBP1mut add an important new diagnostic marker for MDS/MPN and in particular for aCML.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    M Meggendorfer, U Bacher, T Alpermann, C Haferlach, W Kern, T Haferlach & S Schnittger

  2. Department of Health Science, University of Milano-Bicocca, Monza, Italy

    C Gambacorti-Passerini

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Correspondence to S Schnittger.

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TH, WK, CH and SS are part owners of the MLL Munich Leukemia Laboratory GmbH. MM, UB and TA are employed by the MLL Munich Leukemia Laboratory GmbH. CG-P declares no conflict of interest.

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Author contributions

MM investigated molecular mutations, analyzed the data and wrote the manuscript; UB contributed to cytomorphologic analysis and classification of cases and wrote the manuscript; TA collected and documented clinical data and compiled statistical analyses; CG-P originally detected SETBP1 gene mutations and discussed with us this study; WK was involved in statistical analyses; CH was responsible for cytogenetics; TH was responsible for cytomorphologic analysis and was involved in the collection of clinical data; SS was the principal investigator of the study and wrote the manuscript. All authors read and contributed to the final version of the manuscript.

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Meggendorfer, M., Bacher, U., Alpermann, T. et al. SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations. Leukemia 27, 1852–1860 (2013). https://doi.org/10.1038/leu.2013.133

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