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Molecular insight into thiopurine resistance: transcriptomic signature in lymphoblastoid cell lines.


ABSTRACT:

Background

There has been considerable progress in the management of acute lymphoblastic leukemia (ALL) but further improvement is needed to increase long-term survival. The thiopurine agent 6-mercaptopurine (6-MP) used for ALL maintenance therapy has a key influence on clinical outcomes and relapse prevention. Genetic inheritance in thiopurine metabolism plays a major role in interindividual clinical response variability to thiopurines; however, most cases of thiopurine resistance remain unexplained.

Methods

We used lymphoblastoid cell lines (LCLs) from healthy donors, selected for their extreme thiopurine susceptibility. Thiopurine metabolism was characterized by the determination of TPMT and HPRT activity. We performed genome-wide expression profiling in resistant and sen

SUBMITTER: Chouchana L 

PROVIDER: S-EPMC4443628 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature