The purinergic receptor and cytokine receptor-like factor-2 (P2Y Receptor Family Member 8 (P2RY8)::CRLF2) gene fusion has been identified in ~60% of DS-ALL (+21) patients and ~40% of patients with intrachromosomal amplification of chromosome 21 (iAMP21), compared with only 5%–16% of pediatric ALL patients without +21 (7, 8). Here, CRLF2 is linked to acute lymphoblastic leukemia.