Identification of a signature based on non-apoptotic regulatory cell death to improve prognosis prediction in acute myeloid leukaemia

Br J Haematol. 2022 Dec 9. doi: 10.1111/bjh.18601. Online ahead of print.

Abstract

Although anti-apoptotic cell death is a common feature of cancer and non-apoptotic regulatory cell death (RCD) is highly correlated with cancer progression and response to therapy, its prognostic role in patients with acute myeloid leukaemia (AML) is unknown. The RNA sequence and clinical data from AML patients were downloaded from the TCGA and GEO databases. The prognostic characteristics of non-apoptotic RCD-related genes (NRGs) were determined by Cox and LASSO regression analysis. Thirteen NRG signatures were identified as independent prognostic parameters in patients with AML that outperformed other prognostic models. Higher NRG scores were associated with shorter survival and less retention of tumour mutations. Although patients with high NRG risk have abundant signalling pathways for cell adhesion, cytokine upregulation, and cellular defence responses, patients with low NRG risk may benefit the most from immunotherapy. Specifically, patients with high NRG score may benefit from treatment with anti-EGFR and CDK2 inhibitors, including erlotinib and roscovitine. The NPM1 and FLT3 mutant cell lines undergo alterations after multiple drug treatments. Our established NRG signature and scoring highlight its vital clinical significance, emphasize the inevitability of stratifying treatment for different mutation subtypes and provide new ideas to guide personalized immunotherapy strategies for AML patients.

Keywords: acute myeloid leukaemia; immune microenvironment; non-apoptotic regulatory cell death; prognosis; risk score.