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Recurrent MYB rearrangement in blastic plasmacytoid dendritic cell neoplasm

Leukemia volume 31, pages 1629–1633 (2017)Cite this article

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that is derived from plasmacytoid dendritic cell (type 2 dendritic cell) precursors. BPDCN tends to occur in elderly people with frequent skin involvement and is associated with a poor prognosis.1 In the 2016 World Health Organization (WHO) classification, BPDCN was described as a distinct disease and was separately listed among myeloid neoplasms and acute leukemia.2 BPDCN diagnoses in current practice are usually based on clinical manifestations, histopathological features, and patterns of immunophenotypic marker expressions; for example, BPDCNs are generally positive for CD4, CD56, interleukin 3 receptor subunit alpha (also termed CD123), and blood dendritic cell antigen 2 (also termed CD303), and negative for other lineage-specific antigens.1 However, genetic alterations that are diagnostic of BPDCN have not yet been described. Previous studies suggested that acute lymphoblastic leukemia-type multidrug chemotherapy and hematopoietic stem cell transplantation during the first complete remission might improve treatment outcomes with lower rates of relapse and overall mortality, although a standard first-line therapy for BPDCN remains to be determined.1, 3, 4

To date, the pathobiological and genetic aspects of BPDCN remain unclear. In previous studies, BPDCN was associated with peculiar complex karyotypes that affected 5q21 or 5q34 (72%), 12p13 (64%), 13q13–q21 (64%), 6q23–qter (50%), 15q (43%) and the entire chromosome 9 (28%).5 Gene expression profiling of BPDCNs have helped in detecting an aberrant activation of the NF-kB pathway.6 In addition, whole-exome and targeted sequencing analyses revealed recurrent mutations in genes such as TET2, ASXL1 and NPM1 at frequencies of up to 36%, showing some similarity to the spectrum of mutated genes in myelodysplastic syndromes and acute myelogenous leukemia.7 However, there were no commonly shared mutations among the majority of patients.

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Acknowledgements

We thank all of the clinicians, patients and their families who made this study possible with the providing of samples. We also thank Ms. Yoshie Miura, Ms. Yuko Imanishi, Mr Akitaka Sugishita, Ms. Naomi Nomura, and Ms. Hiroe Namizaki for their valuable assistance. We acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for technical support in next-generation sequencing. We also acknowledge the Human Genome Center, Institute of Medical Science, the University of Tokyo (http://sc.hgc.jp/shirokane.html) for providing super-computing resources. This study was supported in part by JSPS KAKENHI Grant Number JP 16H06277 to M.N.

Author contributions

KS, YS, AH, HM, MN and S. Kato designed and performed the research, analyzed the data, and wrote the paper. MG and MI provided samples, performed the research and analyzed the data. DI, MH, RT, SKa, NM, DK, YS and EN performed the research and analyzed the data. NK, AN, NN, YT and SKo designed the research and analyzed the data. YN, HI, SN and KW provided the samples and clinical data. YO led the entire project, designed and performed the research, analyzed the data, and wrote the paper. All authors critically reviewed the content of the manuscript and agreed on the final version of the manuscript.

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Author notes

  1. K Suzuki, Y Suzuki, A Hama, H Muramatsu and M Nakatochi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    K Suzuki, A Hama, H Muramatsu, D Ichikawa, M Hamada, R Taniguchi, S Kataoka, N Murakami, D Kojima, Y Sekiya, E Nishikawa, N Kawashima, A Narita, N Nishio, Y Takahashi & S Kojima

  2. Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan

    Y Suzuki & S Kato

  3. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

    M Nakatochi, N Nishio & Y Okuno

  4. Department of Pathology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    M Gunji & M Ito

  5. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    Y Nakazawa

  6. Department of Pathology, Shizuoka Children’s Hospital, Shizuoka, Japan

    H Iwafuchi

  7. Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    K-i Watanabe

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  1. K Suzuki
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Corresponding authors

Correspondence to S Kato or Y Okuno.

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Competing interests

SKo was supported by a grant from Sanofi KK. KS, YS, AH, MI, SKo, SKa and YO have a patent application related to this paper. The remaining authors declare no conflict of interests.

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Suzuki, K., Suzuki, Y., Hama, A. et al. Recurrent MYB rearrangement in blastic plasmacytoid dendritic cell neoplasm. Leukemia 31, 1629–1633 (2017). https://doi.org/10.1038/leu.2017.101

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