Kappa deleting element as an alternative molecular target for minimal residual disease assessment by real-time quantitative PCR in patients with multiple myeloma.

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.

journal_name

Eur J Haematol

authors

Puig N,Sarasquete ME,Alcoceba M,Balanzategui A,Chillón MC,Sebastián E,Díaz MG,San Miguel JF,García-Sanz R

doi

10.1111/ejh.12000

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

328-35

issue

4

eissn

0902-4441

issn

1600-0609

journal_volume

89

pub_type

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