Format

Send to

Choose Destination
See comment in PubMed Commons below
Blood. 2012 Nov 29;120(23):4513-6. doi: 10.1182/blood-2012-05-426924. Epub 2012 Sep 27.

Sequence analysis of β-subunit genes of the 20S proteasome in patients with relapsed multiple myeloma treated with bortezomib or dexamethasone.

Author information

1
Millennium Pharmaceuticals, 35 Landsdowne St, Cambridge, MA 02139, USA. david.lichter@MPI.com

Abstract

Variations within proteasome β (PSMB) genes, which encode the β subunits of the 20S proteasome, may affect proteasome function, assembly, and/or binding of proteasome inhibitors. To investigate the potential association between PSMB gene variants and treatment-emergent resistance to bortezomib and/or long-term outcomes, in the present study, PSMB gene sequence variation was characterized in tumor DNA samples from patients who participated in the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib versus high-dose dexamethasone for treatment of relapsed multiple myeloma. Twelve new PSMB variants were identified. No associations were found between PSMB single nucleotide polymorphism genotype frequency and clinical response to bortezomib or dexamethasone treatment or between PSMB single nucleotide polymorphism allelic frequency and pooled overall survival or time to progression. Although specific PSMB5 variants have been identified previously in preclinical models of bortezomib resistance, these variants were not detected in patient tumor samples collected after clinical relapse from bortezomib, which suggests that alternative mechanisms underlie bortezomib insensitivity.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00048230.

PMID:
23018640
PMCID:
PMC3757460
DOI:
10.1182/blood-2012-05-426924
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center