Genetic abnormalities including Bmi1 upregulation8–10, homozygous deletion of INK4A/ARF11 and mutations in the lymphoid-lineage transcription factor loci expressing PAX5, IKZF1, and EBF112–14 collaborate with BCR-ABL in the progression to aggressive B-ALL. This evidence concerns the gene IKZF1 and precursor B-cell acute lymphoblastic leukemia.