Fig. 9

Graphical Abstract: Schematic depicting the synergism between IGF2BP1 and ETV6::RUNX1 to Drive Leukemogenesis in B-ALL. IGF2BP1 is overexpressed in ETV6::RUNX1 positive B-ALL cells and it regulates the expression of multiple pro-oncogenic signaling pathways, especially the TNFα/NFκB and PI3K-Akt pathways, by binding and stabilizing its target transcripts. IGF2BP1 also binds and stabilizes the ETV6::RUNX1 fusion transcript, forming a positive feedback loop. Co-expression of ETV6::RUNX1 and IGF2BP1 in murine bone marrow led to clonal expansion of immature progenitors and bone marrow hypercellularity. All these suggest that IGF2BP1 synergizes with ETV6::RUNX1 to drive leukemogenesis in this subtype of B-ALL