AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth
| العنوان: | AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth |
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| المؤلفون: | Ita Novita Sari, Sanghyun Lee, Hyog Young Kwon, Yoseph Toni Wijaya, Nayoung Jun, Kwang Seock Kim, Jeevisha Bajaj, Soo-Hyun Kim, Sa-Hee Park, Tannishtha Reya, Jaeseok Han, Ying-Gui Yang, Vivian G. Oehler, Soo Young Choi, Dong-Wook Kim |
| المصدر: | Oncogene. 40:603-617 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adenosylmethionine Decarboxylase, Cancer Research, Myeloid, Biology, medicine.disease_cause, Mice, Downregulation and upregulation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Genetics, medicine, Animals, Humans, Molecular Biology, Cell Proliferation, Methionine decarboxylase, Myeloid leukemia, medicine.disease, Neoplasm Proteins, Leukemia, medicine.anatomical_structure, Neoplastic Stem Cells, Cancer research, Unfolded protein response, Stem cell, Reactive Oxygen Species, Oxidative stress |
| الوصف: | 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. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::598c9d308d065e7df3f2d3fbe3c5ca53Test https://doi.org/10.1038/s41388-020-01547-xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....598c9d308d065e7df3f2d3fbe3c5ca53 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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