A Novel Prognostic Risk Model for Necroptosis-associated Genes in Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) is a hematological malignancy with high heterogeneity that develops in both children and adults. Necroptosis is a newly recognized form of cell death. Nevertheless, the prognostic significance and functions of necroptosis-related genes (NRGs) in ALL have not received sufficient attention. This study aimed to evaluate the association between NRGs levels and ALL prognosis using publicly available datasets. Methods RNA-sequencing (RNA-seq) data and clinical information for ALL patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Univariate Cox and LASSO regression analyses were applied to select prognosis-related genes for the construction of a prognostic risk-scoring model. Internal and external validation proved the model efficient. Furthermore, we explored the correlation of the prognostic risk model with immune infiltration and drug resistance. Results A total of 7 necroptosis-related genes (NRGs), namely BIRC2, PKP3, MERTK, KL, ESR2, TLE6, and TET2, were used to construct a survival prognostic model. The model exhibited excellent performance in the TARGET cohort and validation group and had good prediction accuracy in screening out high-risk ALL patients. Functional analysis showed that tumor immune microenvironment and drug resistance differed between high- and low-risk groups. Conclusion Our NRGs risk score model is a promising strategy for the prediction of ALL patients’ prognosis.