title: Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest.
abstract: 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.
authors.affiliation: Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, INSERM U1035, Université Bordeaux Ségalen, 146 Rue Léo Saignat Bat TP 4e étage, 33076 Bordeaux, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Drullion
authors.forename: Valérie
authors.initials: V
authors.lastname: Lagarde
authors.forename: Romain
authors.initials: R
authors.lastname: Gioia
authors.forename: Patrick
authors.initials: P
authors.lastname: Legembre
authors.forename: Muriel
authors.initials: M
authors.lastname: Priault
authors.forename: Bruno
authors.initials: B
authors.lastname: Cardinaud
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Jean-Max
authors.initials: JM
authors.lastname: Pasquet