Kappa deleting element as an alternative molecular target for minimal residual disease assessment by real-time quantitative PCR in patients with multiple myeloma.
Eur J Haematol
; 89(4): 328-35, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22805350
ABSTRACT
BACKGROUND AND OBJECTIVES:
Minimal residual disease (MRD) assessment by PCR in multiple myeloma (MM) has several shortcomings, including the lack of a suitable target. Kappa deleting element (KDE) rearrangements occur in virtually all Ig-lambda B-cell malignancies and in 1/3 of Ig-kappa are not affected by somatic hypermutation and, as in ALL, could be used as PCR targets.METHODS:
We have first investigated the incidence, gene segment usage, and CDR3 composition of IGK-KDE rearrangements in 96 untreated myeloma patients. Second, we tested 16 KDE gene rearrangements as molecular targets for MRD assessment by RQ-PCR using a germline reverse primer and a germline Taqman probe in combination with allele-specific oligonucleotides (ASO) as forward primers.RESULTS:
Monoclonal KDE rearrangements were amplified in 45% (43/96) of cases, monoallelic in 2/3 of them (29 cases), and biallellic in the remaining 14 cases. Overall, 88% of cases were successfully sequenced, KDE being equally frequently rearranged with VK and with intron-Recombination signal sequence (RSS). Median numbers of inserted and deleted nucleotides in the junctional region were one and five, respectively.CONCLUSIONS:
Using KDE rearrangements as additional PCR target for MRD assessment in MM improves the applicability of these studies in 9% of cases overall and in 20% of lambda cases. Its use in the latter subset could represent a significant advance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cadeias kappa de Imunoglobulina
/
Neoplasia Residual
/
Reação em Cadeia da Polimerase em Tempo Real
/
Mieloma Múltiplo
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article