Unraveling the Mechanisms of IMP3 Binding Specificity in B-Cell Acute Lymphoblastic Leukemia

Post-transcriptional regulation of gene expression is a complex process involving RNA binding proteins (RBPs) that play a crucial role in mRNA metabolism. RBPs recognize and bind to specific RNA sequences, influencing RNA fate and function. Dysregulation of RBPs has been implicated in various cancers, including hematological malignancies such as B-cell acute lymphoblastic leukemia (B-ALL). The insulin-like growth factor 2 mRNA binding protein 3 (IMP3/IGF2BP3) is an oncofetal RBP that is overexpressed in cancer and has been associated with poor prognosis and resistance to treatment. Despite its significance in cancer, the mechanisms driving IMP3 binding specificity remain poorly understood. In this study, we employed enhanced crosslinking and immunoprecipitation (eCLIP) to investigate the binding specificity of IMP3 in B-ALL cells. By comparing IMP3 targets and binding sites in multiple B-ALL cell lines, we aimed to identify common binding patterns specific to B-ALL and validate genuine leukemogenic IMP3 targets. Our findings shed light on the mechanisms underlying IMP3 binding specificity in B-ALL and provide insights into its role in gene regulation during leukemogenesis. Understanding IMP3-mediated gene regulation in leukemia has the potential to uncover novel therapeutic targets and advance personalized treatment strategies for B-ALL and other cancer types