Elucidating the immune landscape and potential prognostic model in acute myeloid leukemia with TP53 mutation

Autor: Gelan Zhu, Jiayi Cai, Wanbin Fu, Yue Sun, Ting Wang, Hua Zhong
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Hematology, Vol 29, Iss 1 (2024)
Druh dokumentu: article
ISSN: 16078454
1607-8454
DOI: 10.1080/16078454.2024.2400620
Popis: Objectives The TP53 mutation, a prevalent tumor suppressor gene alteration, is linked to chemotherapy resistance, increased relapse rates and diminished overall survival (OS) in acute myeloid leukemia (AML) patients.Methods In this study, we characterize the TP53 mutation phenotypes across various AML cohorts utilizing The Cancer Genome Atlas (TCGA) data. We devised a TP53-related prognostic signature derived from differentially expressed genes between mutated and wild-type TP53 AML specimens. In-depth analyses were conducted, encompassing genetic variation, immune cell infiltration and prognostic stratification.Results A six-gene TP53-related signature was established using least absolute shrinkage and selection operator (LASSO)–Cox regression, demonstrating robust prognostic predictability. This signature exhibited strong performance in both the OHSU validation cohorts, an independent Gene Expression Omnibus (GEO) validation cohort (GSE71014) and proved by results of the in vivo experiment. Finally, we used single cell database (GSE198681) to observe the characteristics of these six genes.Discussion Our study may facilitate the development of efficacious therapeutic approaches and provide a novel idea for future research. Conclusion: The TP53-related signature and pattern hold the potential to refine prognostic stratification and underscore emerging targeted therapies.
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