Functional in vivo characterization of MLL-AF4–regulated miRNAs. miR-128a and miR-130b were identified as MLL-AF4 targets in tumor cells from patients with pediatric B-cell precursor (BCP) ALL. Reconstitution of mice with fetal liver(FL)-derived Mll-AF4⁺ HSPCs induced a pro–B-cell ALL (miR-128a) or a mixed B-cell/myeloid acute leukemia (miR-130b) propagated by Il7r⁺/c-Kit⁺ or LMPP leukemic blasts, respectively. Specific miRNA inhibition or overexpression of hNR2F6 impaired leukemia propagation. Professional illustration by Patrick Lane, ScEYEnce Studios.