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GENOMICS AND GENE THERAPY

Diverse kinase alterations and myeloid-associated mutations in adult histiocytosis

Leukemia volume 36, pages 573–576 (2022)Cite this article

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To the Editor:

Histiocytosis are rare types of hematological tumors originating from dendritic cells or macrophages. Comprehensive genomic analysis have uncovered a series of activating receptor tyrosine kinase alterations in different types of histiocytosis since the discovery of activating MAPK pathway gene mutations in Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), including mutations in BRAF, MAP2K1, ARAF and KRAS [1,2,3,4,5]. In addition, concomitant myeloid malignancies and mutations affecting genes participating in clonal hematopoiesis, such as mutations affecting TET2, ASXL1, and DNMT3A, have been detected in ECD patients [6, 7]. However, most genomic analyses were performed in pediatric patients. Our knowledge about the genetic features and their associated clinical or prognostic significance in adult histiocytosis remains incomplete. Few studies have explored myeloid-associated mutations in other types of histiocytosis except ECD. We thus performed genomic analysis and retrospectively studied the clinical features of adult histiocytosis patients seen in our center over the last fifteen years.

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Fig. 1: Mutational profiles identified by targeted sequencing of 183 genes with FFPE biopsies from histiocytosis patients.

Data availability

The sequencing data obtained in this study were deposited in the Sequence Read Archive (SRA) of NCBI (SRA; accession codes PRJNA672227, PRJNA690872, and PRJNA672228).

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Acknowledgements

The authors thank the patients and their families. This work was supported by institutional research funding provided by the Beijing Natural Science Foundation (Grant No. 7202160 to Cao XX), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (Grant No. 2019-RC-HL-001 to Cao XX).

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  1. These authors contributed equally: Jia Chen, Ai-lin Zhao.

Authors and Affiliations

  1. Department of Hematology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Jia Chen, Ai-lin Zhao, Ming-hui Duan, Hao Cai, Xue-min Gao, Ting Liu, Dao-bin Zhou, Xin-xin Cao & Jian Li

  2. Department of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Ai-lin Zhao

  3. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Jian Sun & Zhi-yong Liang

  4. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Jian Sun, Zhi-yong Liang, Dao-bin Zhou, Xin-xin Cao & Jian Li

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  1. Jia Chen
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Contributions

XXC, JL, DBZ and MHD contributed to study conception and design; ALZ, HC and JC contributed to genomic analysis; ALZ, XMG and TL contributed to patient follow-up; LZ and HCC contributed to data analysis and interpretation; XXC, JL and MHD retrospectively reviewed patient records and contributed to data collection; JC, ALZ and XXC wrote the paper; JS and ZYL reviewed histological findings independently; and all authors revised the paper and approved the submitted version.

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Correspondence to Xin-xin Cao or Jian Li.

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Chen, J., Zhao, Al., Duan, Mh. et al. Diverse kinase alterations and myeloid-associated mutations in adult histiocytosis. Leukemia 36, 573–576 (2022). https://doi.org/10.1038/s41375-021-01439-3

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