Intracellular IL-23R is necessary for mitotic spindle formation and viability in AML
Interleukin-23 receptor (IL-23R) is a cell surface cytokine receptor classically expressed on T cells, where it regulates T cell activation. Here, we discovered a novel intracellular localization and function for IL-23R in Acute Myeloid Leukemia (AML). Compared to normal hematopoietic cells, IL-23R was increased in primary AML samples. IL-23R was predominantly localized intracellularly in AML cells. BioID mass spectrometry identified mitotic spindle proteins as top interactors with IL-23R. We confirmed interaction between endogenous IL-23R and the mitotic spindle in AML cells and primary AML samples, and this interaction was mediated by IL-23R's (S/T)x(I/L)P motif. Genetic depletion of IL-23R disrupted mitotic spindle formation and reduced proliferation and stem cell/progenitor function of AML cell lines and primary AML samples. In contrast, depletion of IL-23R spared normal hematopoietic cells and progenitors. Thus, we discovered a novel intracellular function for IL-23R where this receptor regulates mitotic spindle formation and the growth of AML cells.
Authors
- Karen Fang (ORCID: https://orcid.org/0009-0001-6662-7872)
- Neil MacLean
- Jong Bok Lee (ORCID: https://orcid.org/0000-0002-4744-6021)
- Laura Pascual Matellán (ORCID: https://orcid.org/0000-0002-6897-0148)
- Steven Mitchell Kornblau (ORCID: https://orcid.org/0000-0002-5990-9548)
- Hong Chang (ORCID: https://orcid.org/0000-0003-3106-2776)
- Rose Hurren
- Lan-Xin Zhang (ORCID: https://orcid.org/0000-0002-5918-8082)
- Vito Spadavecchio
- Brian Raught (ORCID: https://orcid.org/0000-0001-6145-4776)
- Courtney L. Jones (ORCID: https://orcid.org/0000-0003-0672-1493)
- Aaron David Schimmer (ORCID: https://orcid.org/0000-0003-4023-3899)
- Stephanie Xie
- Laurence Pelletier (ORCID: https://orcid.org/0000-0003-1171-4618)
- Lily Drimmer
- Nathan Duong (ORCID: https://orcid.org/0000-0001-7171-5554)
- Marcela Gronda
- Dakai Ling
- Andrea Arruda (ORCID: https://orcid.org/0000-0003-2516-8005)
- Yongran Yan (ORCID: https://orcid.org/0009-0005-7337-4331)
- Dilshad H. Khan (ORCID: https://orcid.org/0009-0007-5867-1770)
- Vincent Rondeau (ORCID: https://orcid.org/0000-0002-9513-5703)
- M Minden
- B. W. Brown
- Daniel Goede
- Mary L. Ma
- Yue Feng
- Max G. Jacobs
- Kevin Jacobs
- Li Zhang
- Jonathan St-Germain
- Geethu E. Thomas
Institutions
- Mount Sinai Hospital (CA)
- University Health Network (CA)
- The University of Texas MD Anderson Cancer Center (US)
- University of Toronto (CA)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Toronto General Hospital (CA)
- Princess Margaret Cancer Centre (CA)
- Gamma Therapeutics (United States) (US)
Publication Details
- Journal
- Leukemia
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1038/s41375-026-02949-8
- Primary Topic
- Psoriasis: Treatment and Pathogenesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Princess Margaret Cancer Foundation
- Canadian Institutes of Health Research