CRLF2 alteration is seen at low rates (5–7 %) when all B-ALL cases are grouped together; however, it is seen in 50–60 % of Down Syndrome (DS) associated ALL, suggesting that CRLF2 overexpression is especially relevant to tumorigenesis in patients with trisomy 21 [41–43]. This evidence concerns the gene CRLF2 and precursor B-cell acute lymphoblastic leukemia.