Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells.
Animals
Anti-Ulcer Agents
/ pharmacology
Antimetabolites, Antineoplastic
/ pharmacology
Apoptosis
Carbenoxolone
/ pharmacology
Cell Proliferation
Cytarabine
/ pharmacology
Drug Resistance, Neoplasm
Drug Therapy, Combination
Gap Junctions
/ drug effects
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Mesenchymal Stem Cells
/ cytology
Mice
Mice, Inbred NOD
Mice, SCID
Tumor Cells, Cultured
Tumor Microenvironment
/ drug effects
Xenograft Model Antitumor Assays
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
29
03
2019
accepted:
10
10
2019
revised:
07
10
2019
pubmed:
28
10
2019
medline:
25
11
2020
entrez:
26
10
2019
Statut:
ppublish
Résumé
The bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell-cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34
Identifiants
pubmed: 31649334
doi: 10.1038/s41388-019-1069-y
pii: 10.1038/s41388-019-1069-y
pmc: PMC7002301
doi:
Substances chimiques
Anti-Ulcer Agents
0
Antimetabolites, Antineoplastic
0
Cytarabine
04079A1RDZ
Carbenoxolone
MM6384NG73
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1198-1212Commentaires et corrections
Type : ErratumIn
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