CD69 blockade restores the bone marrow niche and delays leukemogenesis in a mouse model of Nras ^G12D-driven chronic myelomonocytic leukemia.

Authors

Yuchen Li, Xu Jiang, Yinfeng Gu, Xianfeng Zha, Jie Wu, Xiuli Wu, Chunli Qi, Shaohua Chen, Yangqiu Li, Zhenyi Jin, Chengxiang Xia, Ling Xu

Published in

Cancer biology & therapy. Volume 27. Issue 1. Pages 2692184. Dec 31, 2026. Epub Jun 22, 2026.

Abstract

A subset of patients with chronic myelomonocytic leukemia (CMML) carries NRAS mutations, which are associated with shorter overall survival and an increased risk of transformation to acute myeloid leukemia. However, the effects of NRAS mutations on the bone marrow microenvironment (BME) remain unclear.
We used a CMML mouse model driven by a single Nras ^G12D allele mutation to investigate alterations in the BME and the potential role of CD69 in immune suppression. Nras ^G12D-mutated CMML mice were treated with an anti-CD69 monoclonal antibody. Flow cytometry, hematoxylin-eosin staining, and RNA sequencing were performed to evaluate treatment-related changes.
Nras ^G12D-mutated CMML mice showed increased infiltration of regulatory T (Treg) cells and CD69⁺ T cells in the BME, whereas CD69 expression on peripheral blood T cells remained lower than that on bone marrow T cells. Anti-CD69 monoclonal antibody treatment was associated with reduced generation of granulocyte-macrophage progenitor cells, prolonged survival, and decreased Treg accumulation in the BME.
Our findings suggest that CD69 may serve as a biomarker of BME immunological dysfunction in CMML.

PMID:
42330053
Bibliographic data and abstract were imported from PubMed on 23 Jun 2026.

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