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STEM CELL TRANSPLANTATION

Recurrent DDX41 mutation in very late relapse after allogeneic stem cell transplantation

Leukemia volume 38, pages 667–670 (2024)Cite this article

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Relapse after allogeneic stem cell transplantation (SCT) is one of the most common causes of treatment failure. Relapse mainly occurs early after SCT and very late relapse (VLR), defined as a relapse occurring after more than 5 years, is extremely rare. Previous studies on VLR after SCT include only case reports or series with a few cases, and the reports suggested their unique clinical features [1]. Although some previous studies have reported mutation profiles in cases with VLR after chemotherapy or those in cases with early relapse after SCT, the genetic background of VLR after SCT remains to be elucidated [1]. This multicenter retrospective study aimed to elucidate the clinical characteristics and mutation signatures of VLR after SCT.

In this study, tumor samples were retrospectively collected from a total of 25 patients who experienced VLR. The exclusion criteria included patients with donor cell leukemia (DCL). DNA was extracted from each sample, and next-generation sequencing (NGS) targeting 69 myeloid malignancy-associated genes was performed using previously described methods (Supplementary Table 1) [2]. The same analyses were also performed on pre-SCT tumor samples collected from nine patients. Chimerism at VLR was analyzed using commercially available sex chromosome fluorescence in situ hybridization or short tandem repeat method, and/or single-nucleotide polymorphism sequencing with a myeloid panel as previously described [3]. This study was conducted following the Declaration of Helsinki and approved by the Ethics Committee of participating institutions. Written informed consent was obtained from each patient.

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Fig. 1: Mutation landscape of very late relapse cases.
Fig. 2: Clonal evolution of very late relapse cases with DDX41 mutations.

Data availability

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

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Acknowledgements

The authors are grateful to all the participating patients in this study. The authors also thank Kazuteru Ohashi and Keisuke Oboki for management of research environment, and Junko Ohta for her technical assistance. We would like to thank Editage (www.editage.com) for English language editing.

Funding

This research was supported in part by The Japanese Society of Hematology Research Grant and Clinical Research Fund of Tokyo Metropolitan Government.

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Author notes

  1. These authors contributed equally: Yasuhiro Kambara, Daichi Sadato.

Authors and Affiliations

  1. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Yasuhiro Kambara, Takashi Toya, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Hironori Harada & Noriko Doki

  2. Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Daichi Sadato, Chizuko Hirama & Yuka Harada

  3. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Akira Honda & Mineo Kurokawa

  4. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Seiko Kato & Satoshi Takahashi

  5. Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Kyoko Haraguchi & Yoshiki Okuyama

  6. Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Hironori Harada

  7. Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Satoshi Takahashi

  8. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo, Japan

    Mineo Kurokawa

Authors
  1. Yasuhiro Kambara
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  2. Daichi Sadato
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Contributions

YK, DS, TT, and YH designed the study. YK, TT, AH, SK, HS, YN, TK, ST, MK, and ND provided medical treatment to the patients and collected the clinical data. TT, AH, SK, KH, and YO collected clinical samples. DS, CH, and YH performed sequencing analyses. YK, DS, and TT wrote the manuscript and created figures. HH, YH, and ND supervised the study. All the authors have read and approved the manuscript.

Corresponding author

Correspondence to Takashi Toya.

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The authors declare no competing interests.

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Kambara, Y., Sadato, D., Toya, T. et al. Recurrent DDX41 mutation in very late relapse after allogeneic stem cell transplantation. Leukemia 38, 667–670 (2024). https://doi.org/10.1038/s41375-024-02152-7

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