Cyclin D1 mRNA as a molecular marker for minimal residual disease monitoring in patients with mantle cell lymphoma

. 2018 Mar ; 97 (3) : 467-474. [epub] 20171222

Jazyk angličtina Země Německo Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid29273915

Grantová podpora
CZ.2.16/3.1.00/24022 EU-Prague, OPPK
CZ.2.16/3.1.00/2505 EU-Prague, OPPK
GAUK no. 20214 Grantová Agentura, Univerzita Karlova
00064203 Ministerstvo Zdravotnictví Ceské Republiky
PRVOUK P24/LF1/3 Ministerstvo Školství, Mládeže a Tělovýchovy (CZ)
PRVOUK-27/LF1/1 Ministerstvo Školství, Mládeže a Tělovýchovy
NPU I nr.LO1604 Ministerstvo Školství, Mládeže a Tělovýchovy
16-32568A AZV CEP - Centrální evidence projektů
GBP302/12/G101 Grantová Agentura České Republiky

Odkazy

PubMed 29273915
DOI 10.1007/s00277-017-3210-8
PII: 10.1007/s00277-017-3210-8
Knihovny.cz E-zdroje

Chromosomal translocation t(11;14)(q13;q32) is a characteristic molecular marker of mantle cell lymphoma (MCL) and leads to the fusion of the immunoglobulin heavy chain enhancer-promoter with the cyclin D1 gene. Both aberrant cyclin D1 expression and underlying chromosomal aberration may be used as molecular targets for monitoring minimal residual disease (MRD). The present study aims to assess the usefulness of quantitative cyclin D1 gene expression compared to the standardised but more technologically demanding DNA-based method for immunoglobulin heavy chain (IGH) or t(11;14) clone-specific gene rearrangement quantification in a cohort of bone marrow (BM) and peripheral blood (PB) samples from patients with MCL. We simultaneously evaluated DNA-MRD and cyclin D1 expression levels in 234 samples from 57 patients. We observed that both in DNA-MRD positive and negative BM/PB pairs from the same time points the expression levels of cyclin D1 are lower in PB than in BM (median 19×, BM/PB range 0.41-352). The correlation of cyclin D1 transcript levels with DNA-MRD or with flow cytometry was good only in samples with a very high infiltration. In DNA-MRD-negative BM samples, we observed a significant heterogeneity of cyclin D1 expression (in the range of more than three orders of magnitude). This is in contrast to previous reports demonstrating the usefulness of cyclin D1 for MRD monitoring that did not use DNA-based method as a reference. In PB, the specificity of cyclin D1 expression was better due to a lower physiological background. In conclusion, we show that cyclin D1 is unsuitable for MRD monitoring in BM.

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