花生四烯酸促进骨髓增殖性肿瘤中脾脏CD45-Ter119+细胞的髓系分化。
Arachidonic acid promotes myeloid differentiation of splenic CD45- Ter119+ cells in myeloproliferative neoplasm.
作者信息
Zhang Linlin, Yang Yi, Yu Xiao, Li Guodong, Zhang Peihua, Ren Xiaomin, Luo Siyu, Li Lin, Munyurangabo Gustave, Jia Yachun, Song Lingqin, He Aili, Kong Guangyao
机构信息
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
Precision Medical Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
出版信息
J Cancer. 2025 Mar 31;16(7):2289-2297. doi: 10.7150/jca.110478. eCollection 2025.
Although splenic CD45Ter119 cells promote cancer progression by secreting artemin, it remains unclear whether these cells play an important role in myeloproliferative neoplasm (MPN). Here, using a Kras-induced mouse model of MPN, we demonstrated that the number and cycling of CD45Ter119 cells increased in the spleens of MPN mice. Moreover, these cells could differentiate into myeloid cells upon stimulation with GM-CSF and mIL-6. Through RNA sequencing, we further revealed that myeloid genes, such as Hoxa9, Mpo and Ms4a3, were highly expressed in CD45Ter119 cells. Mechanistically, we showed that the arachidonic acid content was significantly elevated in splenic CD45Ter119 cells, and exogenous arachidonic acid mediated the differentiation of splenic CD45Ter119 cells into myeloid cells. Our results revealed that splenic CD45Ter119 cells play a crucial role in myeloid leukemia and that arachidonic acid could be a potential therapeutic target for MPN treatment.
尽管脾脏CD45Ter119细胞通过分泌Artemin促进癌症进展，但这些细胞在骨髓增殖性肿瘤（MPN）中是否发挥重要作用仍不清楚。在此，我们使用Kras诱导的MPN小鼠模型，证明了MPN小鼠脾脏中CD45Ter119细胞的数量和增殖增加。此外，这些细胞在GM-CSF和mIL-6刺激下可分化为髓系细胞。通过RNA测序，我们进一步揭示了Hoxa9、Mpo和Ms4a3等髓系基因在CD45Ter119细胞中高表达。从机制上讲，我们发现脾脏CD45Ter119细胞中花生四烯酸含量显著升高，外源性花生四烯酸介导脾脏CD45Ter119细胞分化为髓系细胞。我们的结果表明，脾脏CD45Ter119细胞在髓系白血病中起关键作用，花生四烯酸可能是MPN治疗的潜在靶点。
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