Effects of the Autophagy-Inhibiting Agent Chloroquine on Acute Myeloid Leukemia Cells; Characterization of Patient Heterogeneity.
acute myeloid leukemia
apoptosis
chemokine
chloroquine
cytokine
proliferation
protein profiling
Journal
Journal of personalized medicine
ISSN: 2075-4426
Titre abrégé: J Pers Med
Pays: Switzerland
ID NLM: 101602269
Informations de publication
Date de publication:
10 Aug 2021
10 Aug 2021
Historique:
received:
14
07
2021
revised:
06
08
2021
accepted:
07
08
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
28
8
2021
Statut:
epublish
Résumé
Autophagy is a highly conserved cellular degradation process that prevents cell damage and promotes cell survival, and clinical efforts have exploited autophagy inhibition as a therapeutic strategy in cancer. Chloroquine is a well-known antimalarial agent that inhibits late-stage autophagy. We evaluated the effects of chloroquine on cell viability and proliferation of acute myeloid leukemia acute myeloid leukemia (AML) cells derived from 81 AML patients. Our results show that chloroquine decreased AML cell viability and proliferation for the majority of patients. Furthermore, a subgroup of AML patients showed a greater susceptibility to chloroquine, and using hierarchical cluster analysis, we identified 99 genes upregulated in this patient subgroup, including several genes related to leukemogenesis. The combination of chloroquine with low-dose cytarabine had an additive inhibitory effect on AML cell proliferation. Finally, a minority of patients showed increased extracellular constitutive mediator release in the presence of chloroquine, which was associated with strong antiproliferative effects of chloroquine as well as cytarabine. We conclude that chloroquine has antileukemic activity and should be further explored as a therapeutic drug against AML in combination with other cytotoxic or metabolic drugs; however, due to the patient heterogeneity, chloroquine therapy will probably be effective only for selected patients.
Identifiants
pubmed: 34442423
pii: jpm11080779
doi: 10.3390/jpm11080779
pmc: PMC8399694
pii:
doi:
Types de publication
Journal Article
Langues
eng
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