miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape

Fang Chen, Dandan Zhao, Yongfang Xu, Yi Zhang, Min-Hsuan Chen, Khyatiben V. Pathak, Nate Hansen, Brooke Lovell, Yong Liang, Katrina Estrella, Wei-Le Wang, Lucy Ghoda, Russell Rockne, Xiwei Wu, Haris Ali, Jianhua Yu, Michael A. Caligiuri, Stephen J. Forman, Jeff M. Trent, Ya-Huei Kuo, Ling Li, Piotr Swiderski, Jianying Zhang, Marcin Kortylewski, Le Xuan Truong Nguyen, Patrick Pirrotte, Mark Boldin, Guido Marcucci () and Bin Zhang ()
Additional contact information
Fang Chen: City of Hope Medical Center and Beckman Research Institute
Dandan Zhao: City of Hope Medical Center and Beckman Research Institute
Yongfang Xu: City of Hope Medical Center and Beckman Research Institute
Yi Zhang: City of Hope Medical Center and Beckman Research Institute
Min-Hsuan Chen: City of Hope Beckman Research Institute
Khyatiben V. Pathak: Translational Genomics Research Institute
Nate Hansen: Translational Genomics Research Institute
Brooke Lovell: Translational Genomics Research Institute
Yong Liang: City of Hope Beckman Research Institute
Katrina Estrella: City of Hope Medical Center and Beckman Research Institute
Wei-Le Wang: City of Hope Beckman Research Institute
Lucy Ghoda: City of Hope Medical Center and Beckman Research Institute
Russell Rockne: City of Hope Beckman Research Institute
Xiwei Wu: City of Hope Beckman Research Institute
Haris Ali: City of Hope Medical Center and Beckman Research Institute
Jianhua Yu: City of Hope National Medical Center
Michael A. Caligiuri: City of Hope National Medical Center
Stephen J. Forman: City of Hope National Medical Center
Jeff M. Trent: Translational Genomics Research Institute
Ya-Huei Kuo: City of Hope Medical Center and Beckman Research Institute
Ling Li: City of Hope Medical Center and Beckman Research Institute
Piotr Swiderski: City of Hope Beckman Research Institute
Jianying Zhang: City of Hope Beckman Research Institute
Marcin Kortylewski: City of Hope Beckman Research Institute
Le Xuan Truong Nguyen: City of Hope Medical Center and Beckman Research Institute
Patrick Pirrotte: Translational Genomics Research Institute
Mark Boldin: City of Hope Beckman Research Institute
Guido Marcucci: City of Hope Medical Center and Beckman Research Institute
Bin Zhang: City of Hope Medical Center and Beckman Research Institute

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells’ metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56383-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56383-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56383-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().