Somatic PAX5 aberrations are evident in ~30% of sporadic B-ALL cases (118) with mechanisms including copy number alterations (often deletion including -9/-9p), translocations generating fusion proteins that retain the DNA binding paired domain and nuclear localization signal of PAX5 (results in a fusion TF that acts as a dominant negative), intragenic amplification (including direct head-to-tail concatenation of exons 2 to 5 resulting in an extra 4-5 copies of the DNA binding and octapeptide domains), disruption to normal alternative splicing and isoform levels, and point mutations (119). Here, PAX5 is linked to precursor B-cell acute lymphoblastic leukemia.