There is evidence that multiple first-hit mutations can change B cell adhesion/migration properties; for example, ETV6::RUNX1 is associated with a cell-intrinsic defect in CXCR4-CXCL12 signaling (35) and KMT2A-mutated BCP-ALL up-regulates protocadherin genes (36). Here, ETV6 is linked to acute lymphoblastic leukemia.