Targeting Chemotherapy to Decondensed H3K27me3-Marked Chromatin of AML Cells Enhances Leukemia Suppression.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
25
04
2021
revised:
15
09
2021
accepted:
03
12
2021
pubmed:
15
12
2021
medline:
16
2
2022
entrez:
14
12
2021
Statut:
ppublish
Résumé
Despite treatment with intensive chemotherapy, acute myelogenous leukemia (AML) remains an aggressive malignancy with a dismal outcome in most patients. We found that AML cells exhibit an unusually rapid accumulation of the repressive histone mark H3K27me3 on nascent DNA. In cell lines, primary cells and xenograft mouse models, inhibition of the H3K27 histone methyltransferase EZH2 to decondense the H3K27me3-marked chromatin of AML cells enhanced chromatin accessibility and chemotherapy-induced DNA damage, apoptosis, and leukemia suppression. These effects were further promoted when chromatin decondensation of AML cells was induced upon S-phase entry after release from a transient G
Identifiants
pubmed: 34903608
pii: 0008-5472.CAN-21-1297
doi: 10.1158/0008-5472.CAN-21-1297
pmc: PMC8889548
mid: NIHMS1765346
doi:
Substances chimiques
Chromatin
0
Histones
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
458-471Subventions
Organisme : NIDDK NIH HHS
ID : F30 DK126356
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226432
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA236736
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257251
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM075141
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127895
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2021 American Association for Cancer Research.
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