• DOI:10.1038/s41388-020-01547-x
• Corpus ID: 226970825

AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth

@article{Sari2020AMD1IR,
  title={AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth},
  author={Ita Novita Sari and Ying-Gui Yang and Yoseph Toni Wijaya and Nayoung Jun and Sanghyun Lee and Kwang Seock Kim and Jeevisha Bajaj and V. G. Oehler and Soo-hyun Kim and Soo Young Choi and Sahee Park and Dong-Wook Kim and Tannishtha Reya and Jaeseok Han and Hyog Young Kwon},
  journal={Oncogene},
  year={2020},
  volume={40},
  pages={603-617}
}

• Ita Novita Sari, Ying-Gui Yang, +12 authors H. Kwon
• Published 17 November 2020
• Biology, Chemistry
• Oncogene

Polyamines are critical elements in mammals, but it remains unknown whether adenosyl methionine decarboxylase (AMD1), a rate-limiting enzyme in polyamine synthesis, is required for myeloid leukemia. Here, we found that leukemic stem cells (LSCs) were highly differentiated, and leukemia progression was severely impaired in the absence of AMD1 in vivo. AMD1 was highly upregulated as chronic myeloid leukemia (CML) progressed from the chronic phase to the blast crisis phase, and was associated with the poor prognosis of CML patients. In addition, the pharmacological inhibition of AMD1 by AO476 treatment resulted in a robust reduction of the progression of leukemic cells both in vitro and in vivo. Mechanistically, AMD1 depletion induced loss of mitochondrial membrane potential and accumulation of reactive oxygen species (ROS), resulting in the differentiation of LSCs via oxidative stress and aberrant activation of unfolded protein response (UPR) pathway, which was partially rescued by the addition of polyamine. These results indicate that AMD1 is an essential element in the progression of myeloid leukemia and could be an attractive target for the treatment of the disease.