IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45737-7.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45737-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45737-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Peng Qiu, 2020. "Embracing the dropouts in single-cell RNA-seq analysis," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    2. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jessica M. Vanslambrouck & Sean B. Wilson & Ker Sin Tan & Ella Groenewegen & Rajeev Rudraraju & Jessica Neil & Kynan T. Lawlor & Sophia Mah & Michelle Scurr & Sara E. Howden & Kanta Subbarao & Melissa, 2022. "Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    2. Ian Covert & Rohan Gala & Tim Wang & Karel Svoboda & Uygar Sümbül & Su-In Lee, 2023. "Predictive and robust gene selection for spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Ziqi Zhang & Haoran Sun & Ragunathan Mariappan & Xi Chen & Xinyu Chen & Mika S. Jain & Mirjana Efremova & Sarah A. Teichmann & Vaibhav Rajan & Xiuwei Zhang, 2023. "scMoMaT jointly performs single cell mosaic integration and multi-modal bio-marker detection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Geert-Jan Huizing & Ina Maria Deutschmann & Gabriel Peyré & Laura Cantini, 2023. "Paired single-cell multi-omics data integration with Mowgli," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Eloise Berson & Anjali Sreenivas & Thanaphong Phongpreecha & Amalia Perna & Fiorella C. Grandi & Lei Xue & Neal G. Ravindra & Neelufar Payrovnaziri & Samson Mataraso & Yeasul Kim & Camilo Espinosa & A, 2023. "Whole genome deconvolution unveils Alzheimer’s resilient epigenetic signature," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Hyun Kim & Won Chang & Seok Joo Chae & Jong-Eun Park & Minseok Seo & Jae Kyoung Kim, 2024. "scLENS: data-driven signal detection for unbiased scRNA-seq data analysis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Jeremie Oliver Piña & Resmi Raju & Daniela M. Roth & Emma Wentworth Winchester & Parna Chattaraj & Fahad Kidwai & Fabio R. Faucz & James Iben & Apratim Mitra & Kiersten Campbell & Gus Fridell & Caroli, 2023. "Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Candace C. Liu & Noah F. Greenwald & Alex Kong & Erin F. McCaffrey & Ke Xuan Leow & Dunja Mrdjen & Bryan J. Cannon & Josef Lorenz Rumberger & Sricharan Reddy Varra & Michael Angelo, 2023. "Robust phenotyping of highly multiplexed tissue imaging data using pixel-level clustering," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45737-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.