α-KGDH–mediated α-KG production is essential for fueling the TCA cycle and maintaining aspartate pools, which are crucial for de novo nucleotide biosynthesis in AML cells. Inhibition of OGDH, the E1 subunit of α-KGDH, disrupts this process, resulting in impaired nucleotide metabolism. This disruption leads to cell cycle arrest, promotes cellular differentiation, and reduces the proliferative capacity of AML cells. The figure was created with BioRender.com.