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

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.

journal_name

Blood

journal_title

Blood

authors

Lichter DI,Danaee H,Pickard MD,Tayber O,Sintchak M,Shi H,Richardson PG,Cavenagh J,Bladé J,Façon T,Niesvizky R,Alsina M,Dalton W,Sonneveld P,Lonial S,van de Velde H,Ricci D,Esseltine DL,Trepicchio WL,Mulligan G,And

doi

10.1182/blood-2012-05-426924

subject

Has Abstract

pub_date

2012-11-29 00:00:00

pages

4513-6

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2012-05-426924

journal_volume

120

pub_type

杂志文章,随机对照试验

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