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Unrelated hematopoietic stem cell transplantation for familial platelet disorder/acute myeloid leukemia with germline RUNX1 mutations

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Abstract

Germline mutations in RUNX1 result in rare autosomal-dominant familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). As genetic analysis is becoming increasingly prevalent, the diagnosis rate of FPD/AML is expected to increase. In this report, we present two pedigrees, one diagnosed molecularly and another highly suspected to be FPD/AML, whose members both received allogeneic hematopoietic stem cell transplantation (HSCT). Both pedigrees had a family history of thrombocytopenia, platelet dysfunction, and hematological malignancies. One family inherited a frameshift mutation (p.P240fs) of RUNX1, a known pathogenic variant. Another family inherited a point mutation (p.G168R) in the runt-homology domain, the clinical significance of which is uncertain at this point. As this mutation was completely absent from all population databases and had a relatively high REVEL score of 0.947, we thought that it would be dangerous to ignore its possible pathogenicity. Consequently, we avoided choosing HSCT donors from relatives of both families and performed HSCT from unrelated donors. In conclusion, our experience with two families of FPD/AML highlights the importance of searching for gene mutations associated with germline predisposition and indicates the necessity of developing a donor coordination system for FPD/AML patients, as well as a support system for families.

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The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank the patients, their families, and all the medical staff members involved in treating these patients. This work was supported by the Department of Pathology and Tumor Biology at Kyoto University. This work was supported by the Japan Agency for Medical Research and Development (AMED) (JP19cm0106501h0004, JP19ck0106250h0003 to S.Ogawa.; JP19ck0106353h0003 to Y.N.), the Japan Society for the Promotion of Science (JSPS); Scientific Research on Innovative Areas (JP15H05909 to S.Ogawa) and KAKENHI (JP26221308 and JP19H05656 to S.Ogawa.; JP18H02836 to Y.N.).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-Cho, Kyoto, Kyoto, 606-8507, Japan

    Kazunori Toratani, Mizuki Watanabe, Junya Kanda, Tomomi Oka, Mizuki Hyuga, Yasuyuki Arai, Makoto Iwasaki, Maki Sakurada & Akifumi Takaori-Kondo

  2. Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan

    Tomomi Oka & Takahiro Yamada

  3. Department of Clinical Laboratory Medicine, Kyoto University, Kyoto, Japan

    Yasuyuki Arai

  4. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan

    Yasuhito Nannya & Seishi Ogawa

  5. Division of Hematopoietic Disease Control, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yasuhito Nannya

Authors
  1. Kazunori Toratani
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  2. Mizuki Watanabe
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  3. Junya Kanda
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  4. Tomomi Oka
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  5. Mizuki Hyuga
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  6. Yasuyuki Arai
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  7. Makoto Iwasaki
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  8. Maki Sakurada
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  9. Yasuhito Nannya
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  10. Seishi Ogawa
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  11. Takahiro Yamada
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  12. Akifumi Takaori-Kondo
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Correspondence to Junya Kanda.

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Toratani, K., Watanabe, M., Kanda, J. et al. Unrelated hematopoietic stem cell transplantation for familial platelet disorder/acute myeloid leukemia with germline RUNX1 mutations. Int J Hematol 118, 400–405 (2023). https://doi.org/10.1007/s12185-023-03575-1

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  • DOI: https://doi.org/10.1007/s12185-023-03575-1

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