We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10<sup>-8</sup>), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10<sup>-8</sup>) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10<sup>-8</sup>), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10<sup>-8</sup>).
These data infer that IGF2BP1 is a potent regulator of ETV6/RUNX1 mRNA stability and potentially link this evolutionary-highly conserved protein to cell transformation events in ETV6/RUNX1-mediated leukemogenesis of t(12;21)(p13;q22)-positive ALL.
To the best of our knowledge, this is the first report of ALL with a 14;17 translocation resulting in an IGH-IGF2BP1 fusion; however, previous studies have implicated a role for up-regulation of IGF2BP1 in ALL.
We show that low/negative IGF2BP1 and IGF2BP3 and high IGF2BP2 levels are characteristic to healthy donor bone marrow and peripheral blood whereas different B-ALL entities displayed characteristic perturbations of IGF2BP expression patterns.