Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.

ABSTRACT: Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume.

SUBMITTER: Feldhahn N 

PROVIDER: S-EPMC3429566 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature