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Re-emergence of acute myeloid leukemia in donor cells following allogeneic transplantation in a family with a germline DDX41 mutation

Leukemia volume 31, pages 520–522 (2017)Cite this article

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Next-generating sequencing (NGS) has helped to reveal the genomic landscape of inherited hematological malignancies. Various genes have recently been identified in families that predispose to increased risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).1, 2 The presentation of the disease varies between the predisposition genes. Recent studies have identified inherited DDX41 mutations in patients with MDS and AML with a latency of disease onset of 62 years.3, 4, 5, 6, 7 This relatively late age of onset might hamper the timely recognition of familial occurrence of MDS and AML, and will probably not restrict donor selection for an allogeneic stem cell transplantation (SCT). This problem is illustrated by the following family history.

To find a genetic explanation for the occurrence of MDS and AML in this family, we performed extensive molecular genetic analyses (Supplementary Information) on the bone marrow of brother C at AML presentation (C1, Table 1) and at MDS relapse (C2), on the peripheral blood of the HLA-matched brother B (B1) and on the peripheral blood of brother A during donor selection (A1) and on his bone marrow cells at AML presentation (A2). In addition, T-cell clones from brothers C (C1T) and A (A2T) were analyzed. SNP array analysis revealed no causal copy number variants in this family.

Table 1 Summary of sampling and detected genetic variants
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Authors and Affiliations

  1. Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    G Berger & E Vellenga

  2. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    E van den Berg, B Sikkema-Raddatz, K M Abbott & R J Sinke

  3. Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    L B Bungener & A B Mulder

Authors
  1. G Berger
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  6. L B Bungener
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Correspondence to E Vellenga.

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Berger, G., van den Berg, E., Sikkema-Raddatz, B. et al. Re-emergence of acute myeloid leukemia in donor cells following allogeneic transplantation in a family with a germline DDX41 mutation. Leukemia 31, 520–522 (2017). https://doi.org/10.1038/leu.2016.310

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