IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51492-6.html
   My bibliography  Save this article

Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia

Author

Listed:
  • Sonali Narang

    (NYU Langone Health)

  • Yohana Ghebrechristos

    (NYU Langone Health
    NYU Langone Health)

  • Nikki A. Evensen

    (NYU Langone Health)

  • Nina Murrell

    (NYU Langone Health
    NYU Langone Health)

  • Sylwia Jasinski

    (NYU Langone Health
    NYU Langone Health)

  • Talia H. Ostrow

    (NYU Langone Health)

  • David T. Teachey

    (Children’s Hospital of Philadelphia)

  • Elizabeth A. Raetz

    (NYU Langone Health
    NYU Langone Health)

  • Timothee Lionnet

    (NYU Langone Health
    NYU Tandon School of Engineering)

  • Matthew Witkowski

    (University of Colorado Anschutz Medical Campus)

  • Iannis Aifantis

    (NYU Langone Health
    NYU Langone Health)

  • Aristotelis Tsirigos

    (NYU Langone Health
    NYU Langone Health)

  • William L. Carroll

    (NYU Langone Health
    NYU Langone Health)

Abstract

Relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains one of the leading causes of cancer mortality in children. We performed Hi-C, ATAC-seq, and RNA-seq on 12 matched diagnosis/relapse pediatric leukemia specimens to uncover dynamic structural variants (SVs) and 3D chromatin rewiring that may contribute to relapse. While translocations are assumed to occur early in leukemogenesis and be maintained throughout progression, we discovered novel, dynamic translocations and confirmed several fusion transcripts, suggesting functional and therapeutic relevance. Genome-wide chromatin remodeling was observed at all organizational levels: A/B compartments, TAD interactivity, and chromatin loops, including some loci shared by 25% of patients. Shared changes were found to drive the expression of genes/pathways previously implicated in resistance as well as novel therapeutic candidates, two of which (ATXN1 and MN1) we functionally validated. Overall, these results demonstrate chromatin reorganization under the selective pressure of therapy and offer the potential for discovery of novel therapeutic interventions.

Suggested Citation

  • Sonali Narang & Yohana Ghebrechristos & Nikki A. Evensen & Nina Murrell & Sylwia Jasinski & Talia H. Ostrow & David T. Teachey & Elizabeth A. Raetz & Timothee Lionnet & Matthew Witkowski & Iannis Aifa, 2024. "Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51492-6
    DOI: 10.1038/s41467-024-51492-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51492-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51492-6?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. Jesse R. Dixon & Siddarth Selvaraj & Feng Yue & Audrey Kim & Yan Li & Yin Shen & Ming Hu & Jun S. Liu & Bing Ren, 2012. "Topological domains in mammalian genomes identified by analysis of chromatin interactions," Nature, Nature, vol. 485(7398), pages 376-380, May.
    2. Jie Li & Phillip M. Galbo & Weida Gong & Aaron J. Storey & Yi-Hsuan Tsai & Xufen Yu & Jeong Hyun Ahn & Yiran Guo & Samuel G. Mackintosh & Ricky D. Edmondson & Stephanie D. Byrum & Jason E. Farrar & Sh, 2021. "ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. William A. Flavahan & Yotam Drier & Brian B. Liau & Shawn M. Gillespie & Andrew S. Venteicher & Anat O. Stemmer-Rachamimov & Mario L. Suvà & Bradley E. Bernstein, 2016. "Insulator dysfunction and oncogene activation in IDH mutant gliomas," Nature, Nature, vol. 529(7584), pages 110-114, January.
    4. Elphège P. Nora & Bryan R. Lajoie & Edda G. Schulz & Luca Giorgetti & Ikuhiro Okamoto & Nicolas Servant & Tristan Piolot & Nynke L. van Berkum & Johannes Meisig & John Sedat & Joost Gribnau & Emmanuel, 2012. "Spatial partitioning of the regulatory landscape of the X-inactivation centre," Nature, Nature, vol. 485(7398), pages 381-385, May.
    5. Charles G. Mullighan & Jinghui Zhang & Lawryn H. Kasper & Stephanie Lerach & Debbie Payne-Turner & Letha A. Phillips & Sue L. Heatley & Linda Holmfeldt & J. Racquel Collins-Underwood & Jing Ma & Kenne, 2011. "CREBBP mutations in relapsed acute lymphoblastic leukaemia," Nature, Nature, vol. 471(7337), pages 235-239, March.
    6. Jie Xu & Fan Song & Huijue Lyu & Mikoto Kobayashi & Baozhen Zhang & Ziyu Zhao & Ye Hou & Xiaotao Wang & Yu Luan & Bei Jia & Lena Stasiak & Josiah Hiu-yuen Wong & Qixuan Wang & Qi Jin & Qiushi Jin & Yi, 2022. "Subtype-specific 3D genome alteration in acute myeloid leukaemia," Nature, Nature, vol. 611(7935), pages 387-398, November.
    7. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
    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. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Jia-Yong Zhong & Longjian Niu & Zhuo-Bin Lin & Xin Bai & Ying Chen & Feng Luo & Chunhui Hou & Chuan-Le Xiao, 2023. "High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Konstantin Okonechnikov & Aylin Camgöz & Owen Chapman & Sameena Wani & Donglim Esther Park & Jens-Martin Hübner & Abhijit Chakraborty & Meghana Pagadala & Rosalind Bump & Sahaana Chandran & Katerina K, 2023. "3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Dunming Hua & Ming Gu & Xiao Zhang & Yanyi Du & Hangcheng Xie & Li Qi & Xiangjun Du & Zhidong Bai & Xiaopeng Zhu & Dechao Tian, 2024. "DiffDomain enables identification of structurally reorganized topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Xiao Ge & Haiyan Huang & Keqi Han & Wangjie Xu & Zhaoxia Wang & Qiang Wu, 2023. "Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Chong Wang & Xiang Liu & Jun Liang & Yohei Narita & Weiyue Ding & Difei Li & Luyao Zhang & Hongbo Wang & Merrin Man Long Leong & Isabella Hou & Catherine Gerdt & Chang Jiang & Qian Zhong & Zhonghui Ta, 2023. "A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Yi Li & James Lee & Lu Bai, 2024. "DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Alon Diament & Tamir Tuller, 2015. "Improving 3D Genome Reconstructions Using Orthologous and Functional Constraints," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-22, May.
    10. Da Lin & Weize Xu & Ping Hong & Chengchao Wu & Zhihui Zhang & Siheng Zhang & Lingyu Xing & Bing Yang & Wei Zhou & Qin Xiao & Jinyue Wang & Cong Wang & Yu He & Xi Chen & Xiaojian Cao & Jiangwei Man & A, 2022. "Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    11. Khalid H. Bhat & Saurabh Priyadarshi & Sarah Naiyer & Xinyan Qu & Hammad Farooq & Eden Kleiman & Jeffery Xu & Xue Lei & Jose F. Cantillo & Robert Wuerffel & Nicole Baumgarth & Jie Liang & Ann J. Feene, 2023. "An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Julia Minderjahn & Alexander Fischer & Konstantin Maier & Karina Mendes & Margit Nuetzel & Johanna Raithel & Hanna Stanewsky & Ute Ackermann & Robert Månsson & Claudia Gebhard & Michael Rehli, 2022. "Postmitotic differentiation of human monocytes requires cohesin-structured chromatin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Wu Zuo & Guangming Chen & Zhimei Gao & Shuai Li & Yanyan Chen & Chenhui Huang & Juan Chen & Zhengjun Chen & Ming Lei & Qian Bian, 2021. "Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    14. Li-Hsin Chang & Sourav Ghosh & Andrea Papale & Jennifer M. Luppino & Mélanie Miranda & Vincent Piras & Jéril Degrouard & Joanne Edouard & Mallory Poncelet & Nathan Lecouvreur & Sébastien Bloyer & Amél, 2023. "Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    15. Jingxuan Xu & Xiang Xu & Dandan Huang & Yawen Luo & Lin Lin & Xuemei Bai & Yang Zheng & Qian Yang & Yu Cheng & An Huang & Jingyi Shi & Xiaochen Bo & Jin Gu & Hebing Chen, 2024. "A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    17. Pengfei Liu & Jeromine Vigneau & Rory J. Craig & Josué Barrera-Redondo & Elena Avdievich & Claudia Martinho & Michael Borg & Fabian B. Haas & Chang Liu & Susana M. Coelho, 2024. "3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Theodore Sakellaropoulos & Catherine Do & Guimei Jiang & Giulia Cova & Peter Meyn & Dacia Dimartino & Sitharam Ramaswami & Adriana Heguy & Aristotelis Tsirigos & Jane A. Skok, 2024. "MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    19. Lina Zheng & Wei Wang, 2022. "Regulation associated modules reflect 3D genome modularity associated with chromatin activity," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Christopher Chase Bolt & Lucille Lopez-Delisle & Aurélie Hintermann & Bénédicte Mascrez & Antonella Rauseo & Guillaume Andrey & Denis Duboule, 2022. "Context-dependent enhancer function revealed by targeted inter-TAD relocation," Nature Communications, Nature, vol. 13(1), pages 1-15, 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_s41467-024-51492-6. 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.