One of the first genome-wide studies in childhood B-ALL described a subgroup of patients harboring a relapse-associated signature characterized by hypermethylation of lymphocyte differentiation related genes (FOXP1, TCF3, BLNK, CD79A, RAG1, and RAG2) and hypomethylation of developmental genes (HOX genes and Polycomb target genes) [49]. Here, TCF3 is linked to precursor B-cell acute lymphoblastic leukemia.