IGF2BP3 Promotes Stemness and Leukemogenesis in Acute Myeloid Leukemia

N6-methyladenosine (m6A) is the most abundant internal modification in mRNA, and its modulators have been implicated in various biological processes. Here, we demonstrate that the mRNA m6A reader IGF2BP3 is highly expressed in human acute myeloid leukemia (AML), particularly in AML leukemia stem/initiating cells (LSCs/LICs). IGF2BP3 is required for the development and maintenance of AML and the self-renewal of LSCs/LICs but dispensable for normal hematopoiesis. IGF2BP3 exhibits promising anti-AML efficacy both in vitro and in vivo, providing new therapeutic strategies for targeting AML. To investigate the impact of IGF2BP3 on gene expression in AML cells, we establised IGF2BP3-knockdown MOLM13 cell lines by two shRNAs together with control MOLM13 cells (shNS), or IGF2BP3-degron U937 cell lines by treated with 5‘-Ph-IAA. We then performed RNA sequencing (RNA-seq) in IGF2BP3-knockdown, IGF2BP3-degron, and control cells.