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Cellular hierarchy insights reveal leukemic stem-like cells and early death risk in acute promyelocytic leukemia

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  • Wen Jin

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yuting Dai

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Li Chen

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Honghu Zhu

    (Beijing Chao-Yang Hospital, Capital Medical University)

  • Fangyi Dong

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Hongming Zhu

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Guoyu Meng

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Junmin Li

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Saijuan Chen

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Zhu Chen

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Hai Fang

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Kankan Wang

    (State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

Abstract

Acute promyelocytic leukemia (APL) represents a paradigm for targeted differentiation therapy, with a minority of patients experiencing treatment failure and even early death. We here report a comprehensive single-cell analysis of 16 APL patients, uncovering cellular compositions and their impact on all-trans retinoic acid (ATRA) response in vivo and early death. We unveil a cellular differentiation hierarchy within APL blasts, rooted in leukemic stem-like cells. The oncogenic PML/RARα fusion protein exerts branch-specific regulation in the APL trajectory, including stem-like cells. APL cohort analysis establishes an association of leukemic stemness with elevated white blood cell counts and FLT3-ITD mutations. Furthermore, we construct an APL-specific stemness score, which proves effective in assessing early death risk. Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.

Suggested Citation

  • Wen Jin & Yuting Dai & Li Chen & Honghu Zhu & Fangyi Dong & Hongming Zhu & Guoyu Meng & Junmin Li & Saijuan Chen & Zhu Chen & Hai Fang & Kankan Wang, 2024. "Cellular hierarchy insights reveal leukemic stem-like cells and early death risk in acute promyelocytic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45737-7
    DOI: 10.1038/s41467-024-45737-7
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    References listed on IDEAS

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    1. Matteo Maria Naldini & Gabriele Casirati & Matteo Barcella & Paola Maria Vittoria Rancoita & Andrea Cosentino & Carolina Caserta & Francesca Pavesi & Erika Zonari & Giacomo Desantis & Diego Gilioli & , 2023. "Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Peng Qiu, 2020. "Embracing the dropouts in single-cell RNA-seq analysis," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
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