Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
LAIR-1 agonism as a therapy for acute myeloid leukemia
Rustin R. Lovewell, … , Dallas B. Flies, Tae Kon Kim
Rustin R. Lovewell, … , Dallas B. Flies, Tae Kon Kim
Published November 15, 2023
Citation Information: J Clin Invest. 2023;133(22):e169519. https://doi.org/10.1172/JCI169519.
View: Text | PDF
Research Article Oncology

LAIR-1 agonism as a therapy for acute myeloid leukemia

  • Text
  • PDF
Abstract

Effective eradication of leukemic stem cells (LSCs) remains the greatest challenge in treating acute myeloid leukemia (AML). The immune receptor LAIR-1 has been shown to regulate LSC survival; however, the therapeutic potential of this pathway remains unexplored. We developed a therapeutic LAIR-1 agonist antibody, NC525, that induced cell death of LSCs, but not healthy hematopoietic stem cells in vitro, and killed LSCs and AML blasts in both cell- and patient-derived xenograft models. We showed that LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells that was enhanced in the presence of collagen. NC525 also significantly improved the activity of azacitidine and venetoclax to establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies.

Authors

Rustin R. Lovewell, Junshik Hong, Subhadip Kundu, Carly M. Fielder, Qianni Hu, Kwang Woon Kim, Haley E. Ramsey, Agnieszka E. Gorska, Londa S. Fuller, Linjie Tian, Priyanka Kothari, Ana Paucarmayta, Emily F. Mason, Ingrid Meza, Yanira Manzanarez, Jason Bosiacki, Karla Maloveste, Ngan Mitchell, Emilia A. Barbu, Aaron Morawski, Sebastien Maloveste, Zac Cusumano, Shashank J. Patel, Michael R. Savona, Solomon Langermann, Han Myint, Dallas B. Flies, Tae Kon Kim

×

Figure 1

LAIR-1 is a target for AML therapy.

Options: View larger image (or click on image) Download as PowerPoint
LAIR-1 is a target for AML therapy.
(A and B) LAIR-1 transcript levels, ...
(A and B) LAIR-1 transcript levels, as measured by RNA sequencing and quantified by RNA Sequencing by Expectation and Maximization (RSEM) software, in AML patient samples clustered by French-American-British (FAB) classification (A) or by molecular mutation (B). UD, undiagnosed (non-AML). n = 1–47 patient samples per group. (C) Illustration of leukemopoiesis from LSC precursors into granulocyte-macrophage progenitor–like (GMP-like) LSCs, lymphoid-primed multipotent progenitor–like (LMPP-like) LSCs, or multipotential progenitor–like (MPP-like) LSCs. (D) Mean fluorescence intensity (MFI) of LAIR-1 cell surface expression on the indicated LSC subpopulations. Each symbol/line represents a unique patient. n = 25 AML patients. (E) Illustration of normal hematopoiesis from hematopoietic stem cells (HSCs) into multipotential progenitors (MPPs), common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), or granulocyte-monocyte progenitors (GMPs). (F) MFI of LAIR-1 cell surface expression on the indicated HSC subpopulations. Each symbol/line represents a unique donor. n = 7 non-AML healthy donors. (G) Comparison of LAIR-1 cell surface expression on cells from comparable compartments from AML patients or healthy donors (H). Each dot represents a unique donor/patient. n = 7 healthy donors or 25 AML patients. P value determined by Student’s t test. Data are shown as the mean ± SEM.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts