Because deletion of Cxcr4 resulted in depletion of MLL-AF9 leukemia cells in serum-free medium without cytokines and because the CXCR4 ligands UBIQUITIN and MIF failed to promote growth and survival of MLL-AF9 leukemia cells by binding to CXCR4, our data suggest that CXCR4 provides baseline signaling independent of ligand stimulation that is sufficient to promote growth and survival of leukemia cells in vivo. Here, MLLT3 is linked to leukemia.