Developmental processes occur as a result of coordinated changes in gene expression, and dysregulated gene expression is at the heart of oncogenic transformation. Simplistically, gene expression can be regulated transcriptionally, at the level of chromatin and transcription factors, and post-transcriptionally, at the level of ribonucleic acid (RNA). The latter element of regulation is now understood to be highly complex and dynamic, and involves the interplay of sequences intrinsic to the regulated RNA molecules and extrinsic factors such as RNA binding proteins (RBPs), microRNAs, and other non-coding RNAs. RBPs have recently emerged as key regulators of post-transcriptional gene regulation, and as such, are likely to have quintessential roles in development and disease. The key to understanding the mechanisms of RBP regulation lies in assessment of the RNA binding repertoires of these RBPs, and meticulously connecting such data to specific points in development and oncogenesis.
Insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an oncofetal RBP with roles in mRNA translation, stabilization and localization. In an effort to understand post-transcriptional regulation of oncogenesis in the B-cell lineage, we undertook a study in B-lymphoblastic leukemia (B-ALL), finding upregulation of IGF2BP3 in cases that carry a translocation of the BLL gene, which portends a bad prognosis. Interestingly, it is dynamically expressed during B-cell development, suggesting a developmental function, and knockdown of IGFBP3 causes decreased growth in B-ALL cell lines. We are currently characterizing the role of this protein in hematopoeitic development and disease.
