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

Abstract

Acute myeloid leukaemia (AML) is a heterogeneous haematologic malignancy characterized by proliferation of nonnormally differentiated myeloblasts or progranulocytes. 1 Five-year survival rates for patients with AML are disappointing at 28.3%, and most cases remain in remission with frequent relapses resulting in a poor prognosis. 2 Recent evidence suggests that the identification of new biomarkers of AML contributes to a better understanding of the molecular basis of the disease and is useful in the detection, diagnosis, prognosis and monitoring of AML and in predicting the likelihood of each individual. 3 Our study aims to construct a new prognostic model and improve risk-adapted treatment for patients.Regulatory cell death (RCD), a fundamental biological phenomenon of cells, has an irreplaceable impact on the onset and development of many processes of life and disease. RCD plays an important role in the stability of homeostasis in vivo, in the development of multiple systems, and the evolution of organisms. 4 Based on different morphological, biochemical, immunological and genetic characteristics, RCD is divided into two categories: apoptotic and non-apoptotic. Non-apoptotic RCD can be subdivided into autophagy, ferroptosis, pyroptosis, necroptosis, and the recently identified cuproptosis. 5,6 Research on apoptosis has been conducted for more than 30 years. However, therapeutic agents targeting apoptosis regulators such as apoptosis-associated cystathionases or B-cell lymphoma 2 (BCL-2) family proteins have been ineffective in anti-tumour therapy. 7 In contrast,