当前位置: X-MOL 学术Cell. Oncol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Comprehensive analysis of clinical prognostic features and tumor microenvironment landscape of CD11b+CD64+ patients with acute myeloid leukemia
Cellular Oncology ( IF 6.6 ) Pub Date : 2023-04-18 , DOI: 10.1007/s13402-023-00808-7
Qian Wang 1 , Nan Zhang 1 , Li Liu 1 , Linlu Ma 1 , Yuxin Tan 1 , Xiaoyan Liu 1 , Jinxian Wu 1 , Guopeng Chen 1 , Xinqi Li 1 , Yuxing Liang 1 , Fuling Zhou 1
Affiliation  

Background

Immunophenotyping surface molecules detected in the clinic are mainly applied in diagnostic confirmation and subtyping. However, the immunomodulatory molecules CD11b and CD64, are highly associated with leukemogenesis. Hence, the prognostic value of them and their potential biological functions merit further investigation.

Methods

Flow cytometry was operated to detect immunophenotypic molecules from AML bone marrow samples. Multivariate cox regression, Kaplan-Meier analyses, and nomogram were conducted to predict survival. Transcriptomic data, lymphocyte subsets, and immunohistochemical staining were incorporated to identify potential biological functions of prognostic immunophenotype in acute myeloid leukemia (AML).

Results

We classified 315 newly diagnosed AML patients of our center based on the expression of CD11b and CD64. The CD11b+CD64+ populations were identified as independent risk factors for overall survival and event-free survival of AML, exhibiting specific clinicopathological features. The predictive models based on CD11b+CD64+ showed high classification performance. In addition, the CD11b+CD64+ subset, characterized by high inhibitory immune checkpoints, M2-macrophage infiltration, low anti-tumor effector cells infiltration, as well as abnormal somatic mutation landscape, presented a distinctive tumor microenvironmental landscape. The CD11b+CD64+ population showd a higher expression of BCL2, and the drug sensitivity indicated that they presented a lower half-maximal inhibitory concentration value for BCL2 inhibitor, and could benefit more from the above medicine.

Conclusions

This work might be of benefit to enhanced understanding of CD11b+CD64+ in the prognosis and leukemogenesis, and yielded novel biomarkers to guide immunotherapy and targeted therapy for AML.



中文翻译:

CD11b+CD64+急性髓系白血病患者临床预后特征及肿瘤微环境格局综合分析

背景

临床检测的免疫表型表面分子主要应用于诊断确认和分型。然而,免疫调节分子 CD11b 和 CD64 与白血病发生高度相关。因此,它们的预后价值及其潜在的生物学功能值得进一步研究。

方法

流式细胞术用于检测 AML 骨髓样本中的免疫表型分子。进行多变量 Cox 回归、Kaplan-Meier 分析和列线图来预测生存率。整合转录组数据、淋巴细胞亚群和免疫组织化学染色来鉴定急性髓系白血病(AML)预后免疫表型的潜在生物学功能。

结果

我们根据CD11b和CD64的表达对我中心的315例新诊断的AML患者进行分类。CD11b + CD64 +人群被确定为 AML 总生存期和无事件生存期的独立危险因素,表现出特定的临床病理学特征。基于CD11b + CD64 +的预测模型表现出较高的分类性能。此外,CD11b + CD64 +亚群以高抑制性免疫检查点、M2巨噬细胞浸润、低抗肿瘤效应细胞浸润以及异常体细胞突变景观为特征,呈现出独特的肿瘤微环境景观。CD11b + CD64 +群体表现出较高的BCL2表达,药物敏感性表明他们对BCL2抑制剂呈现出较低的半最大抑制浓度值,并且可以从上述药物中获益更多。

结论

这项工作可能有助于增强对 CD11b + CD64 +在预后和白血病发生中的认识,并产生新的生物标志物来指导 AML 的免疫治疗和靶向治疗。

更新日期:2023-04-19
down
wechat
bug