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HAL CCSD Résumé : International audience
We used K562 cells sensitive or generated resistant to imatinib or nilotinib to investigate their response to mycophenolic acid (MPA). MPA induced DNA damage leading to cell death with a minor contribution of apoptosis, as revealed by annexin V labeling (up to 25%). In contrast, cell cycle arrest and positive staining for senescence-associated β-galactosidase activity were detected for a large cell population (80%). MPA-induced cell death was potentialized by the inhibition of autophagy and this is associated to the upregulation of apoptosis. In contrast, senescence was neither decreased nor abrogated in autophagy deficient K562 cells. Primary CD34 cells from CML patients sensitive or resistant to imatinib or nilotinib respond to MPA although apoptosis is mainly detected. These results show that MPA is an interesting tool to overcome resistance in vitro and in vivo mainly in the evolved phase of the disease.
Leukemia Research and Treatment
hal-00846103
https://hal.archives-ouvertes.fr/hal-00846103 https://hal.archives-ouvertes.fr/hal-00846103/document https://hal.archives-ouvertes.fr/hal-00846103/file/Mycophenolic_Acid_Overcomes-accepted.pdf PUBMED : 23213550
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