Epigenetic activation of O-linked β-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia.

ABSTRACT:

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 (-)-Δ⁹-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 s

SUBMITTER: Kampa-Schittenhelm KM 

PROVIDER: S-EPMC7139116 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature