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First report of familial mixed phenotype acute leukemia: shared clinical characteristics, Philadelphia translocation, and germline variants

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Abstract

While our understanding of the molecular basis of mixed phenotype acute leukemia (MPAL) has progressed over the decades, our knowledge is limited and the prognosis remains poor. Investigating cases of familial leukemia can provide insights into the role of genetic and environmental factors in leukemogenesis. Although familial cases and associated mutations have been identified in some leukemias, familial occurrence of MPAL has never been reported. Here, we report the first cases of MPAL in a family. A 68-year-old woman was diagnosed with MPAL and received haploidentical stem cell transplantation from her 44-year-old son. In four years, the son himself developed MPAL. Both cases exhibited similar characteristics such as biphenotypic leukemia with B/myeloid cell antigens, Philadelphia translocation (BCR-ABL1 mutation), and response to acute lymphoblastic leukemia-type chemotherapy. These similarities suggest the presence of hereditary factors contributing to the development of MPAL. Targeted sequencing identified shared germline variants in these cases; however, in silico analyses did not strongly support their pathogenicity. Intriguingly, when the son developed MPAL, the mother did not develop donor-derived leukemia and remained in remission. Our cases provide valuable insights to guide future research on familial MPAL.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all the members of our department for their indispensable support.

Funding

The authors did not receive support from any organization for the submitted work.

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Author notes

  1. Yuka Shiozawa and Shinya Fujita contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital, 4-2-22 Nishiki-Cho, Tachikawa-Shi, Tokyo, 190-8531, Japan

    Yuka Shiozawa, Shinya Fujita, Himari Kudo & Takaaki Toyama

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

    Yasuhito Nannya & Seishi Ogawa

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

    Yasuhito Nannya

  4. Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers, Hiroshima, Japan

    Naho Nomura & Nobuo Sezaki

  5. Saitama Medical Center, Department of Diabetes, Endocrinology and Hematology, Dokkyo Medical University, Saitama, Japan

    Toru Kiguchi

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  1. Yuka Shiozawa
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Contributions

YS: Writing—Original Draft. SF: Conceptualization, Methodology, Writing—Review & Editing. YN, SO: Data Curation. NN, TK, NS: Provision of study materials or patients’ information. HK: Modification of manuscript. TT: Supervision. All authors reviewed the manuscript draft and revised it critically on intellectual content. All authors approved the final version of the manuscript to be published.

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Correspondence to Shinya Fujita.

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Shiozawa, Y., Fujita, S., Nannya, Y. et al. First report of familial mixed phenotype acute leukemia: shared clinical characteristics, Philadelphia translocation, and germline variants. Int J Hematol 119, 465–471 (2024). https://doi.org/10.1007/s12185-024-03724-0

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  • DOI: https://doi.org/10.1007/s12185-024-03724-0

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