IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32928-3.html
   My bibliography  Save this article

Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm

Author

Listed:
  • Mohammed Ferdous-Ur Rahman

    (University of Virginia School of Medicine)

  • Yue Yang

    (University of Virginia School of Medicine)

  • Bao T. Le

    (University of Virginia School of Medicine)

  • Avik Dutta

    (University of Virginia School of Medicine)

  • Julia Posyniak

    (University of Virginia School of Medicine)

  • Patrick Faughnan

    (University of Virginia School of Medicine)

  • Mohammad A. Sayem

    (University of Virginia School of Medicine)

  • Nadine S. Aguilera

    (University of Virginia School of Medicine)

  • Golam Mohi

    (University of Virginia School of Medicine
    University of Virginia Cancer Center)

Abstract

Chronic inflammation is frequently associated with myeloproliferative neoplasms (MPN), but the role of inflammation in the pathogenesis of MPN remains unclear. Expression of the proinflammatory cytokine interleukin-1 (IL-1) is elevated in patients with MPN as well as in Jak2V617F knock-in mice. Here, we show that genetic deletion of IL-1 receptor 1 (IL-1R1) normalizes peripheral blood counts, reduces splenomegaly and ameliorates bone marrow fibrosis in homozygous Jak2V617F mouse model of myelofibrosis. Deletion of IL-1R1 also significantly reduces Jak2V617F mutant hematopoietic stem/progenitor cells. Exogenous administration of IL-1β enhances myeloid cell expansion and accelerates the development of bone marrow fibrosis in heterozygous Jak2V617F mice. Furthermore, treatment with anti-IL-1R1 antibodies significantly reduces leukocytosis and splenomegaly, and ameliorates bone marrow fibrosis in homozygous Jak2V617F mice. Collectively, these results suggest that IL-1 signaling plays a pathogenic role in MPN disease progression, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.

Suggested Citation

  • Mohammed Ferdous-Ur Rahman & Yue Yang & Bao T. Le & Avik Dutta & Julia Posyniak & Patrick Faughnan & Mohammad A. Sayem & Nadine S. Aguilera & Golam Mohi, 2022. "Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32928-3
    DOI: 10.1038/s41467-022-32928-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32928-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32928-3?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. Ayuna Hattori & Makoto Tsunoda & Takaaki Konuma & Masayuki Kobayashi & Tamas Nagy & John Glushka & Fariba Tayyari & Daniel McSkimming & Natarajan Kannan & Arinobu Tojo & Arthur S. Edison & Takahiro It, 2017. "Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia," Nature, Nature, vol. 545(7655), pages 500-504, May.
    2. Lorena Arranz & Abel Sánchez-Aguilera & Daniel Martín-Pérez & Joan Isern & Xavier Langa & Alexandar Tzankov & Pontus Lundberg & Sandra Muntión & Yi-Shiuan Tzeng & Dar-Ming Lai & Jürg Schwaller & Radek, 2014. "Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms," Nature, Nature, vol. 512(7512), pages 78-81, August.
    3. Nicholas Williams & Joe Lee & Emily Mitchell & Luiza Moore & E. Joanna Baxter & James Hewinson & Kevin J. Dawson & Andrew Menzies & Anna L. Godfrey & Anthony R. Green & Peter J. Campbell & Jyoti Nanga, 2022. "Life histories of myeloproliferative neoplasms inferred from phylogenies," Nature, Nature, vol. 602(7895), pages 162-168, February.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shivam Rai & Elodie Grockowiak & Nils Hansen & Damien Luque Paz & Cedric B. Stoll & Hui Hao-Shen & Gabriele Mild-Schneider & Stefan Dirnhofer & Christopher J. Farady & Simón Méndez-Ferrer & Radek C. S, 2022. "Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    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. Yash Pershad & Taralynn Mack & Hannah Poisner & Yasminka A. Jakubek & Adrienne M. Stilp & Braxton D. Mitchell & Joshua P. Lewis & Eric Boerwinkle & Ruth J. F. Loos & Nathalie Chami & Zhe Wang & Kathle, 2024. "Determinants of mosaic chromosomal alteration fitness," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Alicia Villatoro & Vincent Cuminetti & Aurora Bernal & Carlos Torroja & Itziar Cossío & Alberto Benguría & Marc Ferré & Joanna Konieczny & Enrique Vázquez & Andrea Rubio & Peter Utnes & Almudena Tello, 2023. "Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    3. Diletta Fontana & Ilaria Crespiatico & Valentina Crippa & Federica Malighetti & Matteo Villa & Fabrizio Angaroni & Luca De Sano & Andrea Aroldi & Marco Antoniotti & Giulio Caravagna & Rocco Piazza & A, 2023. "Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Raymond K. H. Yip & Joel S. Rimes & Bianca D. Capaldo & François Vaillant & Kellie A. Mouchemore & Bhupinder Pal & Yunshun Chen & Elliot Surgenor & Andrew J. Murphy & Robin L. Anderson & Gordon K. Smy, 2021. "Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis," IJERPH, MDPI, vol. 19(24), pages 1-57, December.
    6. Tea Pemovska & Johannes W. Bigenzahn & Ismet Srndic & Alexander Lercher & Andreas Bergthaler & Adrián César-Razquin & Felix Kartnig & Christoph Kornauth & Peter Valent & Philipp B. Staber & Giulio Sup, 2021. "Metabolic drug survey highlights cancer cell dependencies and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    7. Derek W. Brown & Liam D. Cato & Yajie Zhao & Satish K. Nandakumar & Erik L. Bao & Eugene J. Gardner & Aubrey K. Hubbard & Alexander DePaulis & Thomas Rehling & Lei Song & Kai Yu & Stephen J. Chanock &, 2023. "Shared and distinct genetic etiologies for different types of clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Shivam Rai & Elodie Grockowiak & Nils Hansen & Damien Luque Paz & Cedric B. Stoll & Hui Hao-Shen & Gabriele Mild-Schneider & Stefan Dirnhofer & Christopher J. Farady & Simón Méndez-Ferrer & Radek C. S, 2022. "Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Heather E. Machado & Nina F. Øbro & Nicholas Williams & Shengjiang Tan & Ahmed Z. Boukerrou & Megan Davies & Miriam Belmonte & Emily Mitchell & E. Joanna Baxter & Nicole Mende & Anna Clay & Philip Anc, 2023. "Convergent somatic evolution commences in utero in a germline ribosomopathy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Giulia Schiroli & Vinay Kartha & Fabiana M. Duarte & Trine A. Kristiansen & Christina Mayerhofer & Rojesh Shrestha & Andrew Earl & Yan Hu & Tristan Tay & Catherine Rhee & Jason D. Buenrostro & David T, 2024. "Cell of origin epigenetic priming determines susceptibility to Tet2 mutation," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:13:y:2022:i:1:d:10.1038_s41467-022-32928-3. 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.