Prior to advances in next-generation sequencing (NGS) technology, ETV6::RUNX1, TCF3::PBX1, hyperdiploidy (>50 chromosomes), and a trisomy of chromosomes 4, 10 and 17 were known markers of favorable outcomes, whereas the lysine methyltransferase 2A (KMT2A) (previously known as mixed-lineage leukemia or MLL) rearrangement, Philadelphia chromosome-positive (Ph+) (characterized by translocation 9;22), the intrachromosomal amplification of chromosome 21, and hypoploidy were considered unfavorable markers in patients with B-ALL. This evidence concerns the gene TCF3 and acute lymphoblastic leukemia.