Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Acta Haematol. 2022;145(6):627-641. doi: 10.1159/000526346. Epub 2022 Aug 5.
The aim of the study was to construct a pyroptosis-related risk score (RS) model for the prognosis of acute myeloid leukemia (AML).
The TARGET (training) and E-MTAB-1216 (validation) datasets were downloaded. Pyroptosis-related genes with differences in expression were identified between the recurrent and nonrecurrent samples of the training dataset. An RS prognostic model comprising seven pyroptosis-related genes was constructed using LASSO regression coefficients. The samples were classified into the high- and low-risk groups using the RS model; the differentially expressed genes (DEGs) between these groups were identified, followed by DEG functional analysis and the immunological evaluation of these groups.
Forty-nine pyroptosis-related genes, including 22 DEGs, were screened. WT1, NPM, FLT3/ITD, and CEBPA mutations were found in most pediatric AML samples. An RS prognostic model was constructed using 7 pyroptosis-related genes. The two risk groups and prognostic data were significantly related. FLT3/ITD mutations, CEBPA mutations, and RS model status were identified as independent prognostic factors, using the clinical information. The DEGs between the two groups were correlated with immune-related pathways. Moreover, the immune cell distribution and the occurrence of immune-related pathways were notably decreased in the high-risk group.
DISCUSSION/CONCLUSION: Seven pyroptosis-related genes, CHMP2A, PRKACA, CASP9, IRF2, CHMP3, HMGB1, and AIM2, can predict the prognosis and recurrence of childhood AML.
本研究旨在构建急性髓系白血病（AML）预后相关的细胞焦亡风险评分（RS）模型。
下载 TARGET（训练）和 E-MTAB-1216（验证）数据集。鉴定训练数据集复发性和非复发性样本之间表达差异的细胞焦亡相关基因。使用 LASSO 回归系数构建包含七个细胞焦亡相关基因的 RS 预后模型。使用 RS 模型将样本分为高低风险组；鉴定两组间差异表达基因（DEGs），随后对这些基因进行 DEG 功能分析和免疫评价。
筛选出 49 个细胞焦亡相关基因，包括 22 个 DEGs。大多数儿科 AML 样本中存在 WT1、NPM、FLT3/ITD 和 CEBPA 突变。使用 7 个细胞焦亡相关基因构建 RS 预后模型。两个风险组和预后数据显著相关。FLT3/ITD 突变、CEBPA 突变和 RS 模型状态被确定为独立的预后因素，与临床信息有关。两组间的 DEGs 与免疫相关通路相关。此外，高危组的免疫细胞分布和免疫相关通路的发生明显减少。
讨论/结论：七个细胞焦亡相关基因，CHMP2A、PRKACA、CASP9、IRF2、CHMP3、HMGB1 和 AIM2，可预测儿童 AML 的预后和复发。
