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Multi-omics analysis identifies an M-MDSC-like immunosuppressive phenotype in lineage-switched AML with KMT2A rearrangement

Author

Listed:
  • Takashi Mikami

    (Kyoto University)

  • Itaru Kato

    (Kyoto University)

  • Akira Nishimura

    (Institute of Science Tokyo)

  • Minenori Eguchi-Ishimae

    (Ehime University Graduate School of Medicine)

  • Tatsuya Kamitori

    (Kyoto University)

  • Keiji Tasaka

    (Kurashiki Central Hospital)

  • Hirohito Kubota

    (Kyoto University)

  • Tomoya Isobe

    (University of Cambridge)

  • Yoshinori Uchihara

    (Kyoto University)

  • Yui Namikawa

    (Institute of Science Tokyo)

  • Satoru Hamada

    (University of the Ryukyus)

  • Shinichi Tsujimoto

    (Yokohama City University Graduate School of Medicine)

  • Shotaro Inoue

    (Kobe University Graduate School of Medicine
    Kobe Children’s Hospital)

  • Takayuki Hamabata

    (Kurashiki Central Hospital)

  • Kazushi Izawa

    (Kyoto University)

  • Takako Miyamura

    (the University of Osaka Graduate School of Medicine)

  • Daisuke Tomizawa

    (National Center for Child Health and Development)

  • Toshihiko Imamura

    (Kyoto Prefectural University of Medicine)

  • Hidemi Toyoda

    (Mie University Graduate School of Medicine)

  • Mariko Eguchi

    (Ehime University Graduate School of Medicine)

  • Hiroaki Goto

    (Kanagawa Children’s Medical Center)

  • Seishi Ogawa

    (Kyoto University
    Institute for the Advanced Study of Human Biology (WPI-ASHBi)
    Karolinska Institute)

  • Masatoshi Takagi

    (Institute of Science Tokyo)

  • James Badger Wing

    (Osaka University
    Osaka University
    Center for Advanced Modalities and DDS (CAMaD), Osaka University)

  • Junko Takita

    (Kyoto University)

Abstract

Lineage switching (LS) is the conversion of cancer cell lineage during the course of a disease. LS in leukemia cell lineage facilitates cancer cells escaping targeting strategy like CD19 targeted immunotherapy. However, the genetic and biological mechanisms underlying immune evasion by LS leukemia cells are not well understood. Here, we conduct a multi-omics analysis of patient samples and find that lineage-switched acute myeloid leukemia (LS AML) cells with KMT2A rearrangement (KMT2A-r) possess monocytic myeloid derived suppressor cell (M-MDSC)-like characteristics. Single-cell mass cytometry analysis reveals an increase in the M-MDSC like LS AML as compared to those of lineage-consistent KMT2A-r AML, and single-cell transcriptomics identify distinct expression patterns of immunoregulatory genes within this population. Furthermore, in vitro assays confirm the immunosuppressive capacity of LS AML cells against T cells, which is analogous to that of MDSCs. These data provide insight into the immunological aspects of the complex pathogenesis of LS AML, as well as development of future treatments.

Suggested Citation

  • Takashi Mikami & Itaru Kato & Akira Nishimura & Minenori Eguchi-Ishimae & Tatsuya Kamitori & Keiji Tasaka & Hirohito Kubota & Tomoya Isobe & Yoshinori Uchihara & Yui Namikawa & Satoru Hamada & Shinich, 2025. "Multi-omics analysis identifies an M-MDSC-like immunosuppressive phenotype in lineage-switched AML with KMT2A rearrangement," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63271-y
    DOI: 10.1038/s41467-025-63271-y
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