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Epigenetic activation of O-linked Î2-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia by Kampa-Schittenhelm, K.M.; Haverkamp, T.; Bonin, M.; Tsintari, V.; BÃ1⁄4hring, H.J.; Haeusser, L.; Blumenstock, G.; Dreher, S.T.; Ganief, T.; Akmut, F.; Illing, B.; Mau-Holzmann, U.A.; Bonzheim, I.; Schleicher, E.; Vogel, W.; Schittenhelm, M.M. is a Medicine article available to read on EtoBox.
What is Epigenetic activation of O-linked Î2-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia about?
## Background Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy – now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA)-based regimens. Similar approaches in other leukemia subtypes, such as IDH1/2-mutated AML, are under active investigation. We herein present successful release of the differentiation blockage upon treatment with the natural (−)-Δ^9^-Tetrahydrocannabinol isomer dronabinol __in vitro__ and __in vivo__. ## Methods Cellular maturation and differentiation were followed in two patients employing whole genome methylation profiling, proteome analyses, NGS deep sequencing and multispectral imaging flow cytometry. For functional studies lentiviral OGT knock-down __in vitro__ and __ex vivo__ cell models were created to evaluate proliferative, apoptotic and differentiating effects of OGT in acute leukemia. ## Findings In here, we provide molecular evidence that dronbinol is capable to override the differentiation blockage of acute leukemia blasts at the state of the leukemia-initiating clone. We further identify the O-linked β-__N__-a
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- Author
- Kampa-Schittenhelm, K.M.; Haverkamp, T.; Bonin, M.; Tsintari, V.; BÃ1⁄4hring, H.J.; Haeusser, L.; Blumenstock, G.; Dreher, S.T.; Ganief, T.; Akmut, F.; Illing, B.; Mau-Holzmann, U.A.; Bonzheim, I.; Schleicher, E.; Vogel, W.; Schittenhelm, M.M.
- Publisher
- Elsevier ; Elsevier BV; Amsterdam: Elsevier (ISSN 2352-3964)
- Published
- 2020
- Language
- EN
- Field
- Medicine (Life Sciences)