Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Practice, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2024 Sep 12;15:1408109. doi: 10.3389/fimmu.2024.1408109. eCollection 2024.
Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8 T cells and the prognosis of AML patients. To develop a CD8 T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8 T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8 T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8 T and CD8 T groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8 T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.
尽管基因组学和表观遗传学研究的进展加深了我们对急性髓细胞白血病 (AML) 的理解,但只有三分之一的患者能够实现持久缓解。越来越多的证据表明,骨髓中的免疫微环境会影响 AML 患者的预后和生存。CD8 T 细胞与 AML 患者的预后有特定的关联。为了开发与 CD8 T 细胞相关的 AML 免疫风险评分,我们首先评估了 CIBERSORTx 在预测 bulk RNA-seq 中 CD8 T 细胞丰度方面的准确性,发现它与观察到的单细胞 RNA 测序数据和流式细胞术衍生的 CD8 T 细胞比例显著相关。接下来,我们使用 CD8 T 和 CD8 T 组之间差异表达基因的单变量和 LASSO 回归构建了 CTCG15,这是一个 15 个基因的预后标志。CTCG15 在不同平台的六个数据集上得到了进一步验证。CTCG15 独立于已建立的预后标志物,能够提取与 AML 患者预后密切相关的几种遗传异常的转录组后果。最后,将该模型整合到 2022 年欧洲白血病网中,有助于提高预后预测的预测能力。总之,我们的研究表明,CD8 T 细胞相关特征可以改善 AML 的综合风险分层和预后预测。