Acute myeloid leukemia (AML) is an aggressive hematological malignancy frequently exhibiting deregulated expression/activity/localization of the Wnt signaling mediator -catenin.To derive more effective -catenin targeting strategies, we previously interrogated its interaction network in myeloid cells and identified several putative novel interacting partners, including Target of EGR1 (TOE1); a deadenylase with unknown function in hematological tissue.This study aimed to define TOE1 function in hematopoietic cells and uncover its molecular targets.TOE1 interacted with -catenin in both primary and immortalized AML cells, and impacted Wnt signaling output through the modulation of lymphoid enhancer-binding factor-1 (LEF-1).AML samples exhibited deregulated TOE1 expression versus normal hematopoietic stem/progenitor cells (HSPCs), and TOE1 depletion suppressed the proliferation of myeloid leukemia cell lines, and primary human HSPCs, partly through a p21-activated-kinase 2 (PAK2) mediated mechanism.In summary, these data reveal TOE1 as a novel regulator of hematopoietic cell proliferation via the modulation of important growth-regulating pathways.
Park et al. (Wed,) studied this question.