Serial xenotransplantation of primary leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC; however, its expression was upregulated in MA4+ blasts infiltrating extramedullar hematopoietic sites and CNS, which was confirmed by in vivo loss-of-function assays and by a migratory transcriptomic signature of NG2+ MLLr blasts. Here, CSPG4 is linked to leukemia.