Research SummaryRole of IGF2BP1, an RNA binding protein, in lymphomagenesis
B-cell acute lymphoblastic leukemia/lymphoma (ALL) is a disease of the pediatric age group and is a major health problem worldwide. 50% of B-ALL tumors exhibit chromosomal rearrangements with ETV6-RUNX1 being the commonest.
RNA binding proteins (RBPs) regulate gene expression post-transcriptionally. Our preliminary study identified an RBP IGF2BP1 (Insulin like Growth Factor 2 mRNA Binding Protein 1) to be highly expressed in B-ALL with ETV6-RUNX1 translocations. IGF2BP1 has previously been implicated in multiple epithelial tumors.
Our knowledge about the linkage behind ETV6-RUNX1 translocation and RBP IGF2BP1 overexpression is deficient. Hence, we are attempting to answer the following research questions: Does IGF2BP1 expression correlate with disease progression? Does it synergize with ETV6-RUNX1 to cause leukemia? Being an RNA binding protein what are its direct targets in B-ALL? Can IGF2BP1 knockdown be a viable option to treat B-ALL?
Our project hopes to define the clinical significance of IGF2BP1 in B-ALL, establish the RNA binding footprint for this protein and describe its mechanism of action in malignant transformation. Once the importance of IGF2BP1 in leukemogenesis is proven conclusively, it can be used as a diagnostic biomarker and possibly a therapeutic target in ETV6-RUNX1 positive B-ALL.
Figure Legend: We hypothesize that the fusion protein ETV6-RUNX1 synergizes with IGF2BP1 to augment an oncogenic gene network leading to frank leukemia. Our study hopes to validate this theory.