This review analyzes the role of cytokines and chemokines such as IL-6, TNF-α, and CXCL12, which act as biological biomarkers and key mediators of leukemia niche remodeling, and the main signaling pathways involved in ALL, such as Wnt/β-catenin, JAK/STAT, PI3K/AKT/mTOR, Notch, and BCR, highlighting their functional interconnection with the tumor microenvironment. This evidence concerns the gene TNF and leukemia.