Table of Contents
Leukemia Research and Treatment
Volume 2012, Article ID 861301, 9 pages
Research Article

Mycophenolic Acid Overcomes Imatinib and Nilotinib Resistance of Chronic Myeloid Leukemia Cells by Apoptosis or a Senescent-Like Cell Cycle Arrest

1Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, INSERM U1035, Université Bordeaux Ségalen, 146 Rue Léo Saignat Bat TP 4e étage, 33076 Bordeaux, France
2IRSET, EA 4427 SERAIC, Université Rennes-1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France
3IBGC, UMR CNRS 5095, Université Bordeaux Ségalen, 1 Rue Camille Saint Saëns, 33077 Bordeaux, France

Received 30 September 2011; Accepted 16 November 2011

Academic Editor: Judith E. Karp

Copyright © 2012 Claire Drullion et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.