A highly sensitive and specific qPCR assay for quantification of the biomarker SOX11 in mantle cell lymphoma

Objectives Mantle cell lymphoma ( MCL ) is one of the most heterogeneous lymphoid neoplasms with a variable course of disease. Although t(11;14)(q13;q32) is the hallmark of MCL resulting in cyclin D1 ( CCND 1 ) overexpression in 90% of patients, this is difficult to validate by immunohistochemistry. We hypothesised that SOX 11 could be a robust molecular biomarker for MCL . Methods We have developed very sensitive and specific RT‐ qPCR assay employing a poly‐A specific RT primer to circumvent contamination from gDNA caused by the intron‐less nature of SOX11 . Results We found a significant difference between the expression levels of SOX 11 in patients with MCL at diagnosis ( n  =   21) and in healthy donors ( n  =   18) (blood: P  <   0.0001; marrow: P  =   0.0001). SOX 11 expression of very low levels close to the assay sensitivity was detected in only 2 of 18 healthy donors, while low levels of CCND 1 expression was observed in all blood and 12 of 13 marrow samples within the defined detection limit of Cq = 40. In spiking experiments of the GRANTA ‐519 MCL cell line into mononuclear cells from normal donor, the sensitivity of the SOX 11 assay was found to be 2 × 10 −4 , while the sensitivity of the CCND 1 assay was estimated to 2 × 10 −3 because of the normal background expression. In longitudinal sampling from patients with MCL the minimal residual disease ( MRD ) values based on the SOX 11 expression mirrored the clinical disease development. Conclusion This SOX11 RT‐qPCR assay could be a useful tool for MRD monitoring in patients with MCL.