MT1E in AML: a gateway to understanding regulatory cell death and immunotherapeutic responses

Author:

Zhuang Xin1ORCID,Chen Peng1,Yang Kaiqian1,Yang Rong1,Man Xiaoying1,Wang Ruochen1,Shi Yifen12

Affiliation:

1. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province 325000 , China

2. Qinghai Province Women and Children's Hospital , Xining, Qinghai Province 810000 , China

Abstract

Abstract Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration. We combined TCGA and GTEx data, analyzing 1,488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression. We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML vs healthy bone marrow (P < 0.05). Consequently, experiments were designed to assess the function of MT1E overexpression. Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion (P < 0.001), decreased migration (P < 0.001), and invasiveness (P < 0.05), and increased apoptosis (P < 0.05), with a notable rise in Caspase3 expression. A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.

Funder

Natural Science Foundation of Zhejiang Province

Public Welfare Science and Technology Project of Wenzhou

Zhejiang Provincial Clinical Research Center for Hematological Disorders

Publisher

Oxford University Press (OUP)

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