OGFOD1: a critical mediator of chemoresistance in acute myeloid leukemia

2-oxoglutarate-and iron-dependent oxygenase domain-containing protein 1(OGFOD1) is a prolyl hydroxylase that plays a pivotal role in regulating protein synthesis accuracy and efficiency. OGFOD1 is implicated in the pathogenesis of various cancers, including lung cancer, breast cancer and colonic cancer. A recent study highlights that under chemotherapy pressure, the upregulation of OGFOD1 promotes global protein synthesis via its catalytic activity, which is a key mechanism for AML chemoresistance. Deleting of OGFOD1 specifically compromises AML translation adaptability, thereby eradicating post-chemotherapy resistant cells and extending survival in vivo, while sparing normal hematopoiesis. Consequently, targeting OGFOD1 with identified inhibitors presents a promising therapeutic strategy to disrupt the translational adaptability of AML cells, potentially overcoming chemoresistance and improving patient outcomes. More importantly, there is an urgent need to develop highly selective OGFOD1-targeted agents with minimal toxicity.