Reduced ATXN1 expression as an adverse prognostic indicator in Acute myeloid leukemia

Acute myeloid leukemia (AML), a heterogeneous hematopoietic malignancy, continues to present significant challenges in clinical management due to its unfavorable prognosis despite advances in therapy. The identification of novel molecular markers remains essential for improving prognostic stratification and guiding therapeutic decision-making.

ATXN1 expression, its prognostic significance, and associated immune infiltration patterns in AML were systematically evaluated using bioinformatic analyses of The Cancer Genome Atlas (TCGA) and independent validation cohorts. A prognostic nomogram incorporating ATXN1 expression was developed to estimate survival outcomes. The functional role of ATXN1 was further examined in vitro using proliferation and colony formation assays.

ATXN1 expression was significantly downregulated in AML relative to normal hematopoietic cells (p < 0.001). Decreased ATXN1 expression was associated with inferior overall survival across multiple datasets (TCGA, p = 0.023) and was associated with prognosis in multivariate analysis adjusted for age and sex (p = 0.03). Gene set enrichment analysis identified pathways related to cysteine metabolism and immune regulation associated with ATXN1 expression. Immune profiling demonstrated a positive correlation between higher ATXN1 expression and monocyte infiltration (R = 0.42, p < 0.001), along with enhanced activity of immune cell populations, including macrophages, neutrophils, and dendritic cells. Functional assays demonstrated that ATXN1 overexpression suppressed proliferation and colony formation in AML cell lines.

ATXN1 represents a potential prognostic marker in AML, with reduced expression associated with adverse clinical outcomes and transcriptomic features suggestive of immune-related alterations. Further investigation is needed to determine whether ATXN1-associated pathways represent viable therapeutic targets.