Cooperativity of IGF2BP1 and ETV6-RUNX1 in the pathogenesis of ETV6-RUNX1 positive B-Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy with ETV6-RUNX1 being the most prevalent translocation. However, the exact pathogenesis of this translocation remains unclear. Insulin like Growth Factor 2 Binding Protein 1 (IGF2BP1), an oncofetal RNA binding protein, is known to be overexpressed in ETV6-RUNX1 positive B-ALL. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RNA Immunoprecipitation sequencing (RIP-Seq) after pulldown of IGF2BP1 revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including the TNFa/NFkB and PI3K pathways. Together, our data suggest a synergistic impact of ETV6-RUNX1 fusion protein and IGF2BP1 in targeting oncogenic pathways and contributing to the pathogenesis of ALL.