Characterization of newly established Pralatrexate-resistant cell lines and the mechanisms of resistance.

ABSTRACT:

Background

Pralatrexate (PDX) is a novel antifolate approved for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma, but some patients exhibit intrinsic resistance or develop acquired resistance. Here, we evaluated the mechanisms underlying acquired resistance to PDX and explored potential therapeutic strategies to overcome PDX resistance.

Methods

To investigate PDX resistance, we established two PDX-resistant T-lymphoblastic leukemia cell lines (CEM and MOLT4) through continuous exposure to increasing doses of PDX. The resistance mechanisms were evaluated by measuring PDX uptake, apoptosis induction and folate metabolism-related protein expression. We also applied gene expression analysis and methylation profiling to identify the mechanisms of res

SUBMITTER: Oiwa K 

PROVIDER: S-EPMC8325835 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature