天津医药

天津医药 ›› 2026, Vol. 54 ›› Issue (3): 225-231.doi: 10.11958/20252591

• 细胞与分子生物学 •    下一篇

Let-7b诱导白血病相关巨噬细胞复极抑制AML的发展

姜天佑(), 李敏, 孙碧文, 李越洋, 邢丽静, 田晨△()   

  1. 天津医科大学肿瘤医院血液科，国家恶性肿瘤临床医学研究中心，天津市恶性肿瘤临床医学研究中心，天津市肿瘤防治重点实验室（邮编300060）
  • 收稿日期:2025-07-25 修回日期:2025-11-10 出版日期:2026-03-15 发布日期:2026-03-17
  • 通讯作者: E-mail：tianchen@tjmuch.com
  • 作者简介:姜天佑（1973），男，主治医师，主要从事血液肿瘤的诊治方面研究。E-mail：446926319@qq.com
  • 基金资助:
    新疆维吾尔自治区自然科学基金(2022D01A09)

Let-7b inhibits the development of AML through inducing repolarization of leukemia-associated macrophages

JIANG Tianyou(), LI Min, SUN Biwen, LI Yueyang, XING Lijing, TIAN Chen△()   

  1. Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
  • Received:2025-07-25 Revised:2025-11-10 Published:2026-03-15 Online:2026-03-17
  • Contact: E-mail：tianchen@tjmuch.com

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摘要：

目的 研究白血病相关巨噬细胞（LAM）通过let-7b调控急性髓系白血病（AML）的机制。方法 治疗前采集AML患者骨髓细胞保存，给予患者“DA 3+7”方案诱导治疗后评价疗效，分为完全缓解（CR）组和未完全缓解（难治）组。将预保存的患者骨髓AML细胞分别回输到NOD/SCID小鼠，由此建立CR组和难治组的AML小鼠模型。经微RNA（miRNA）测序和实时定量聚合酶链反应（RT-qPCR）验证，选择let-7b为靶基因，研究其在AML中的作用。构建let-7b小分子干扰RNA（shRNA）转染MLL-AF9诱导的AML小鼠的LAM细胞，应用RT-qPCR、蛋白质印迹法、酶联免疫吸附试验（ELISA）和体内体外实验进行验证。结果 相较AML CR组，AML难治组中LAM细胞凋亡率较低。干扰MLL-AF9诱导的AML小鼠骨髓LAM中let-7b，可促进LAM向M1亚型特征分化并激活核因子（NF）-κB通路，白血病细胞的增殖受抑，向脾的浸润下降，抑制AML进展。结论 干扰LAM中的let-7b后可活化Toll样受体（TLR）和NF-κB通路，促使LAM向M1型巨噬细胞复极，从而抑制AML的发展。

关键词: 白血病, 髓样, 急性, 肿瘤相关巨噬细胞, NF-κB, Toll样受体, let-7b, 白血病相关巨噬细胞

Abstract:

Objective To study the mechanism of let-7b regulating acute myeloid leukemia (AML) by leukemia-associated macrophages (LAMs). Methods Bone marrow cells were collected from AML patients prior to any treatment and cryopreserved. Patients subsequently received induction chemotherapy with the "DA 3+7" regimen, and therapeutic responses were evaluated post-treatment. According to the efficacy assessment results, patients were stratified into two groups: the complete remission (CR) group and the non-complete remission (refractory) group. AML blasts of pre-cryopreserved patients were then respectively transplanted into NOD/SCID mice to establish AML xenograft mouse model corresponding to the CR group and the refractory group. After miRNA sequencing and polymerase chain reaction (PCR) verification, let-7b was selected as the target gene to investigate its role in MLL-AF9-induced AML. Transfection of LAMs in MLL-AF9-induced AML mice with let-7b shRNA or scramble control was validated by quantitative real-time PCR (RT-qPCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) in vitro and in vivo experiments. Results Compared with the AML CR group, the apoptosis rate of LAM cells was lower in the AML refractory group. Furthermore, let‐7b was a potentially aberrant gene in LAMs contributing to M2‐subtype characteristics. Knockdown of let‐7b in LAMs could inhibit the development of AML by repolarizing LAMs toward M1‐subtype characteristics through the activation of Toll‐like receptor and NF‐κB pathway. The results of in vivo experiments showed that knockdown of let-7b in LAMs inhibited the proliferation of leukemia cells and decreased infiltration into spleen, thereby inhibiting the progression of AML. Conclusion Let-7b interference in LAMs can activate Toll-like receptors (TLRs) and NF-κB pathway, promote the repolarization of LAMs to M1 macrophages, thereby inhibiting the development of AML.

Key words: leukemia, myeloid, acute, tumor-associated macrophages, NF-kappa B, Toll-like receptors, let-7b, leukemia-associated macrophages

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