An ssGSEA analysis on the cell lines’ transcriptomic data revealed that TNF-α signaling via NF-κB—one of the few Cancer Hallmarks that presented differential enrichment scores across the cell lines overexpressed in BCP-ALL compared to T-ALL—was also directly associated with the activation of NF-κB by TNF-α, cell proliferation, and MTX resistance, confirming the crosstalk between the expression of the signaling pathway and the phenotypic traits. This evidence concerns the gene NFKB1 and cancer.