AKR1C enzymes sustain therapy resistance in paediatric T-ALL.

ABSTRACT:

Background

Despite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (T-ALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors.

Methods

Expression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL. The effects of AKR1C enzyme modulation has been investigated in T-ALL cell lines and primary cultures by combining AKR1C inhibition, overexpression, and gene silencing approaches.

Results

We show that T-ALL cells overexpress AKR1C1-3 enzymes in therapy

SUBMITTER: Bortolozzi R 

PROVIDER: S-EPMC5931104 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature