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Novel RUNX1 mutations in familial platelet disorder with enhanced risk for acute myeloid leukemia: clues for improved identification of the FPD/AML syndrome

Leukemia volume 24, pages 242–246 (2010)Cite this article

Familial aggregation of leukemia is rare. In some families, however, a clear segregation of the predisposition to leukemia is observed. A prime example is familial platelet disorder in which the affected individuals exhibit an enhanced risk to develop acute myeloid leukemia (FPD/AML). This condition is characterized by thrombocytopenia, platelet dysfunction and a 35% lifetime risk for developing leukemia.1

FPD/AML is caused by germline mutations in RUNX1.2 The encoded RUNX1 protein contains a highly conserved Runt domain, which is involved in both DNA binding and heterodimerization with its partner protein, CBFβ. Together these proteins form a transcription factor complex that is widely expressed in various hematopoietic lineages and regulates the expression of several critical genes.3

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Acknowledgements

We are grateful to all patients for their participation in this study. The Affymetrix array analyses in pedigree 2 were performed by the Australian Genome Research Facility, which was established through the Commonwealth-funded Major National Research Facilities program. MCJ Jongmans is an MD-medical research trainee, sponsored by The Netherlands Organisation for Health Research and Development. This work was also supported by grants from the National Health and Medical Research Council of Australia to HSS (program Grants 257501 and 219176, fellowships 171601 and 461204), and a Dora Lush Postgraduate Award (CLC), a Leukaemia Foundation of Australia (grant-in-aid to HSS, postdoctoral fellowship to CLC), the Cancer Council of South Australia (HSS), and MedVet Pty Ltd (HSS).

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Author notes

  1. H S Scott and N Hoogerbrugge: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    M C J Jongmans, R P Kuiper, E Kamping, E F P M Schoenmakers, A Geurts van Kessel & N Hoogerbrugge

  2. Department of Molecular Medicine, Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Victoria, Australia

    C L Carmichael, E J Wilkins, A Carmagnac & H S Scott

  3. Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia

    C L Carmichael & H S Scott

  4. Department of Pediatric Oncology, Emma Children,

    N Dors & A Y N Schouten-van Meeteren

  5. ′,

    N Dors & A Y N Schouten-van Meeteren

  6. s Hospital Academic Medical Center, Amsterdam, The Netherlands

    N Dors & A Y N Schouten-van Meeteren

  7. Department of Molecular Pathology, The Centre for Cancer Biology, Institute of Medical and Veterinary Science, The Hanson Institute, Adelaide, South Australia, Australia

    X Li, M Stankovic, C N Hahn & H S Scott

  8. Adelaide Cancer Research Institute, The School of Medicine, University of Adelaide, South Australia, Australia

    X Li, M Stankovic, C N Hahn & H S Scott

  9. Life Sciences Division, Department of Statistics, University of California, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    H Bengtsson

  10. Department of Pediatric Hemato-oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    P M Hoogerbrugge & P P Brons

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  1. M C J Jongmans
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  12. E F P M Schoenmakers
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  13. A Geurts van Kessel
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Corresponding authors

Correspondence to M C J Jongmans or H S Scott.

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Jongmans, M., Kuiper, R., Carmichael, C. et al. Novel RUNX1 mutations in familial platelet disorder with enhanced risk for acute myeloid leukemia: clues for improved identification of the FPD/AML syndrome. Leukemia 24, 242–246 (2010). https://doi.org/10.1038/leu.2009.210

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