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A novel pedigree with heterozygous germline RUNX1 mutation causing familial MDS-related AML: can these families serve as a multistep model for leukemic transformation?

Leukemia volume 23, pages 1364–1366 (2009)Cite this article

The runt-related transcription factor 1 (RUNX1) encodes for an α-subunit of the core-binding factor and is known as the key regulator in myeloid cells. Heterozygous germline mutations in RUNX1 were identified as a causative genetic alteration leading to a familial platelet disorder with propensity to myeloid malignancies (FPD/MM). For the development of overt leukemia, secondary alterations are required.1 To discuss the potential use of FPD/MM as a multistep model for leukemic transformation in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), we report here on a female index patient and her father, who both developed MDS-related AML (MDR-AML) with differing clinical course caused by a heterozygous germline mutation in RUNX1 and different secondary chromosomal aberrations.

Analysis of RUNX1 identified the heterozygous germline mutation c.520C>T, p.Arg174X in the index patient and her father (Figure 1b). The frameshift mutation with a predicted dominant negative effect2 was earlier found in another family with FPD/MM and a sporadic case of atypical CML with acquired trisomy 21.3, 4

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Acknowledgements

We thank the patients for their participation in this study, Friederike Grundstedt and Marcel Tauscher for their expert technical assistance, and Gillian Teicke for her assistance in editing the paper. This work was supported by the European Genomic and Epigenetic Study on MDS and AML (EuGESMA) COST action network. TR was supported by a grant from the MD/PhD Program Molecular Medicine, Hannover Medical School.

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Authors and Affiliations

  1. Hannover Medical School, Institute of Cell and Molecular Pathology, Hannover, Germany

    T Ripperger, D Steinemann, G Göhring & B Schlegelberger

  2. Department of Hematology and Oncology, University of Freiburg, Freiburg, Germany

    J Finke

  3. Division of Pediatric Hematology-Oncology, Department of Pediatric and Adolescent Medicine, University of Freiburg, Freiburg, Germany

    C M Niemeyer & B Strahm

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  1. T Ripperger
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  2. D Steinemann
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  3. G Göhring
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  7. B Schlegelberger
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Correspondence to B Schlegelberger.

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Ripperger, T., Steinemann, D., Göhring, G. et al. A novel pedigree with heterozygous germline RUNX1 mutation causing familial MDS-related AML: can these families serve as a multistep model for leukemic transformation?. Leukemia 23, 1364–1366 (2009). https://doi.org/10.1038/leu.2009.87

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