Identification of characteristic IGF2BP expression patterns in distinct B-ALL entities

Abstract

Insulin-like growth factor 2 mRNA-binding proteins IGF2BP1, IGF2BP2, and IGF2BP3 have been shown to have diagnostic and prognostic utility in a number of epithelial and soft tissue tumors. Still, little is known about the expression of these molecules in different types of leukemia and our study aims to fill this gap. By using an RT-qPCR approach, we have systemically analyzed the expression of three IGF2BP coding genes in normal hematopoietic tissues and distinct acute lymphoblastic leukemia (ALL) entities. We show that low/negative IGF2BP1 and IGF2BP3 and high IGF2BP2 levels are characteristic to healthy donor bone marrow and peripheral blood whereas different B-ALL entities displayed characteristic perturbations of IGF2BP expression patterns. Namely, we have identified significant associations of overexpressed IGF2BP1 with ETV6/RUNX1-positive (r(2)=0.7891, y=0.8105x-0.4471, p<0.0001), underexpressed IGF2BP2 with E2A/PBX1-positive (p<0.01), and overexpressed IGF2BP2 and IGF2BP3 with MLL/AF4-positive (r(2)=0.6571, y=0.1507x-0.2722, p<0.0001, and r(2)=0.7022, y=0.6482x-0.7660, p<0.0001, respectively) leukemia. Secondly, based on transcript expression dynamics during follow-up, we conclude that overexpression of only IGF2BP1 is inherent characteristic of ETV6/RUNX1-positive leukemic blasts in contrast to IGF2BP3 which remained stably expressed throughout the monitoring period and upon the achievement of molecular remission. Finally, our data suggest that IGF2BP3 might be a marker of disease aggressiveness in BCR/ABL1-positive ALL as consistently increasing levels of this transcript during follow-up predicted eventual leukemia relapse by three months. Altogether, our results highlight the potential utility of IGF2BP profiling in precursor B lymphoid neoplasms as the functions of IGF2BPs in normal and malignant hematopoiesis are further delineated.