Artikel ; Online: Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia
EMBO Molecular Medicine, Vol 14, Iss 7, Pp n/a-n/a (2022)
2022
Abstract: Abstract The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate‐limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins, and phospholipids. ...
| Abstract | Abstract The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate‐limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins, and phospholipids. DHODH inhibitors (DHODHi) are clinically used for autoimmune diseases and are emerging as a novel class of anticancer agents, especially in acute myeloid leukemia (AML) where pyrimidine starvation was recently shown to reverse the characteristic differentiation block in AML cells. Herein, we show that DHODH blockade rapidly shuts down protein translation in leukemic stem cells (LSCs) and has potent and selective activity against multiple AML subtypes. Moreover, we find that ablation of CDK5, a gene that is recurrently deleted in AML and related disorders, increases the sensitivity of AML cells to DHODHi. Our studies provide important molecular insights and identify a potential biomarker for an emerging strategy to target AML. |
|---|---|
| Schlagwörter | acute myeloid leukemia ; DHODH ; leukemic stem cells ; protein translation ; Medicine (General) ; R5-920 ; Genetics ; QH426-470 |
| Sprache | Englisch |
| Erscheinungsdatum | 2022-07-01T00:00:00Z |
| Verlag | Wiley |
| Dokumenttyp | Artikel ; Online |
| Datenquelle | BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl) |
Volltext online
Zusatzmaterialien
Kategorien
Fernleihe an ZB MED
Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.