RNA Targeting in Acute Myeloid Leukemia.
Journal
ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411
Informations de publication
Date de publication:
11 Dec 2020
11 Dec 2020
Historique:
received:
26
08
2020
entrez:
21
12
2020
pubmed:
22
12
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Nucleosides and their analogues constitute an essential family of anticancer drugs. DNA has been the presumptive target of the front-line prodrug for acute myeloid leukemia (AML), cytarabine (ara-C), since the 1980s. Here, the biomolecular targeting of ara-C was evaluated in primary white blood cells using the ara-C mimic "AzC" and azide-alkyne "click" reactions. Fluorescent staining and microscopy revealed that metabolic incorporation of AzC into primary white blood cells was unexpectedly enhanced by the DNA polymerase inhibitor aphidicholine. According to RNaseH digestion and pull-down-and-release experiments, AzC was incorporated into short RNA fragments bound to DNA in peripheral blood monocytes (PBMCs) collected from all six healthy human donors tested. Samples from 22 AML patients (French-American-British classes M4 and M5) exhibited much more heterogeneity, with 27% incorporating AzC into RNA and 55% into DNA. The overall survival of AML patients whose samples incorporated AzC into RNA was approximately 3-fold higher as compared to that of the DNA cohort (
Identifiants
pubmed: 33344899
doi: 10.1021/acsptsci.0c00120
pmc: PMC7737216
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1225-1232Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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