IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia

Abstract

The oncofetal protein insulin-like growth factor 2 mRNA-binding protein 3 (<i>IGF2BP3</i>) belongs to a family of RNA-binding proteins involved in localization, stability, and translational regulation of target RNAs. <i>IGF2BP3</i> is used as a diagnostic and prognostic marker in several malignancies. Although the prognosis of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved, a subgroup of patients exhibits high-risk features and suffer from disease recurrence. We sought to identify additional biomarkers to improve diagnostics, and we assessed expression of <i>IGF2BP3</i> in a population-based pediatric cohort of B-ALL using a tissue microarray platform. The majority of pediatric B-ALL cases were positive for <i>IGF2BP3</i> immunohistochemistry and were associated with an increased proliferative phenotype and activated STAT5 signaling pathway. Two large gene expression data sets were probed for the expression of <i>IGF2BP3</i>-the highest levels were seen among the B-cell lymphomas of a germinal center origin and well-established (KMT2A-rearranged and ETV6-RUNX1) and novel subtypes of B-ALL (e.g., NUTM1 and ETV6-RUNX1-like). A high mRNA for <i>IGF2BP3</i> was associated with a proliferative "metagene" signature and a high expression of <i>CDK6</i> in B-ALL. A low expression portended inferior survival in a high-risk cohort of pediatric B-ALL. Overall, our results show that <i>IGF2BP3</i> shows subtype-specificity in expression and provides prognostic utility in high-risk B-ALL.